Ablation catheter having a shape memory stylet

ABSTRACT

An ablation apparatus for creating a lesion in target tissue, the ablation apparatus having an ablation shaft including a handle, a first portion, an ablation portion, distal tip, at least one ablation energy delivery lumen, at least one ablation energy return lumen, and a stylet lumen that extends substantially along a length of the ablation shaft from the handle to at least the ablation portion. The ablation apparatus also includes a stylet that is capable of being inserted into the stylet lumen where the stylet is made of a shape-memory material.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims the benefit of (i) U.S. Provisional ApplicationNo. 62/554,483, filed Sep. 5, 2017, (ii) U.S. Provisional ApplicationNo. 62/575,998, filed Oct. 23, 2017 and (iii) U.S. ProvisionalApplication No. 62/669,039, filed May 9, 2018. The entire contents ofeach provisional application are incorporated herein by reference intheir entirety for all purposes.

BACKGROUND 1. Field of the Invention

Embodiments of the invention relate to cryosurgery and more particularlyto cryoablation systems and catheters for the treatment of heartdisease.

2. Description of the Related Art

Atrial flutter and atrial fibrillation are heart conditions in which theleft or right atrium of the heart beat improperly. Atrial flutter is acondition when the atria beat very quickly, but still evenly. Atrialfibrillation is a condition when the atria beat very quickly, butunevenly.

These conditions are often caused by aberrant electrical behavior ofsome portion of the atrial wall. Certain parts of the atria, or nearbystructures such as the pulmonary veins, can misfire in their productionor conduction of the electrical signals that control contraction of theheart, creating abnormal electrical signals that prompt the atria tocontract between normal contractions caused by the normal cascade ofelectrical impulses. This can be caused by spots of ischemic tissue,referred to as ectopic foci, or by electrically active fibers in thepulmonary veins, for example.

Ventricular tachycardia (V-tach or VT) is a type of regular and fastheart rate that arises from improper electrical activity in theventricles of the heart. In ventricular tachycardia, the abnormalelectrical signals in the ventricles cause the heart to beat faster thannormal, usually 100 or more beats a minute, out of sync with the upperchambers. When this happens, the heart may not be able to pump enoughblood to the body and lungs because the chambers are beating so fast orout of sync with each other that the chambers do not have time to fillproperly. Thus, V-tach may result in cardiac arrest and may turn intoventricular fibrillation.

Atrial fibrillation is one of the more prevalent types of heartconditions. Failing to treat atrial fibrillation can lead to a number ofundesirable consequences including heart palpitations, shortness ofbreath, weakness and generally poor blood flow to the body.

Various techniques are practiced to treat atrial fibrillation. Onetechnique to treat AF is pulmonary vein isolation (PVI). PVI isperformed by creating lesions circumscribing the pulmonary veins. ThePVI serves to block the errant or abnormal electrical signals.

A challenge in performing PVI, however, is to obtain a lasting orpermanent isolation of the pulmonary veins. This shortcoming ishighlighted in various studies. In one long-term follow-up study thatinvestigated the rate of pulmonary vein reconnection after initialisolation, 53% of 161 patients were free of AF. In 66 patients, a repeatablation was performed for repeat arrhythmia. The rate of pulmonary veinreconnection was high at 94% (62 of 66 patients). (Ouyang F, Tilz R,Chun J, et al. Long-term results of catheter ablation in paroxysmalatrial fibrillation: lessons from a 5-year follow-up. Circulation 2010;122:2368-77.)

One reason that some PVI treatments are not durable is because of thephenomena of pulmonary vein (or electrical) reconnection. (Sawhney N,Anousheh R, Chen W C, et al. Five-year outcomes after segmentalpulmonary vein isolation for paroxysmal atrial fibrillation. Am JCardiol 2009; 104:366-72) (Callans D J, Gerstenfeld E P, Dixit S, et al.Efficacy of repeat pulmonary vein isolation procedures in patients withrecurrent atrial fibrillation. J Cardiovasc Electrophysiol 2004;15:1050-5) (Verma A, Kilicaslan F, Pisano E, et al. Response of atrialfibrillation to pulmonary vein antrum isolation is directly related toresumption and delay of pulmonary vein conduction. Circulation 2005;112:627-35)

Pulmonary vein reconnection may be attributed to gaps and incomplete ordiscontinuous isolation of the veins. (Bunch T J, Cutler M J. Ispulmonary vein isolation still the cornerstone in atrial fibrillationablation? J Thorac Dis. 2015 February; 7(2):132-41). Incompleteisolation is a result of residual gap(s) within the encircling lesion orlack of transmural lesions. (McGann C J, Kholmovski E G, Oakes R S, etal. New magnetic resonance imaging-based method for defining the extentof left atrial wall injury after the ablation of atrial fibrillation. JAm Coll Cardiol 2008; 52:1263-71.) (Ranjan R, Kato R, Zviman M M, et al.Gaps in the ablation line as a potential cause of recovery fromelectrical isolation and their visualization using MRI. Circ ArrhythmElectrophysiol 2011; 4:279-86.)

Additionally, early recurrence of AF post ablation may be an earlymarker of incomplete pulmonary vein isolation. This is supported by astudy of 12 patients that underwent a maze procedure after a failedradiofrequency ablation. Notably, myocardial biopsies showed anatomicgaps and/or non-transmural lesions in pulmonary veins that hadreconnected. (Kowalski M, Grimes M M, Perez F J, et al. Histopathologiccharacterization of chronic radiofrequency ablation lesions forpulmonary vein isolation. J Am Coll Cardiol 2012; 59:930-8.)

This is further supported in a canine study in which endocardialconduction block was demonstrated and post procedural gaps wereidentified using MRI within the line of ablation. Long-term follow updata demonstrated that those pulmonary veins with the MRI-identifiedgaps were more likely to become electrically reconnected withsymptomatic recurrences. (Ranjan R, Kato R, Zviman M M, et al. Gaps inthe ablation line as potential cause of recovery from electricalisolation and their visualization using MRI. Circ ArrhythmElectrophysiol 2011; 4:279-86.)

Various attempts to solve the above referenced problem include makinglinear ablations in combination with circumferential pulmonary veinisolation (CPVI). One study, for example, compared clinical outcomes ofCPVI with additional linear ablations and CPVI in a prospectiverandomized controlled study among patients with paroxysmal AF. The studyenrolled 100 paroxysmal AF patients (male 75.0%, 56.4±11.6 years old)who underwent radio frequency circumferential ablation (RFCA) and wererandomly assigned to the CPVI group (n=50) or the catheter Dallas lesiongroup (CPVI, posterior box lesion, and anterior linear ablation, n=50).The catheter Dallas lesion group required longer procedure (190.3±46.3vs. 161.1±30.3 min, P<0.001) and ablation times (5345.4±1676.4 vs.4027.2±878.0 s, P<0.001) than the CPVI group. Complete bidirectionalconduction block rate was 68.0% in the catheter Dallas lesion group and100% in the CPVI group. Procedure-related complication rates were notsignificantly different between the catheter Dallas lesion (0%) and CPVIgroups (4%, P=0.157). During the 16.3±4.0 months of follow-up, theclinical recurrence rates were not significantly different between thetwo groups, regardless of complete bidirectional conduction blockachievement after linear ablation. (Kim et al. Linear ablation inaddition to circumferential pulmonary vein isolation (Dallas lesion set)does not improve clinical outcome in patients with paroxysmal atrialfibrillation: a prospective randomized study. Europace. 2015 March;17(3):388-95.)

Thus, in view of the above referenced study, adding more ablation pointsaround the vein entries, and/or attempting to add a linear lesion byusing point by point ablation, does not appear to be an optimal solutionto prevent gap(s) along the encircling lesion. Additionally, addingmultiple points and lines undesirably increases the procedure time.

In view of the above shortcomings, various ablation catheters have beenproposed for creation of the lesion, including flexible cryoprobes orcryocatheters, bipolar RF catheters, monopolar RF catheters (usingground patches on the patient's skin), microwave catheters, lasercatheters, and ultrasound catheters. U.S. Pat. No. 6,190,382 to Ormsbyand U.S. Pat. No. 6,941,953 to Feld, for example, describe RF ablationcatheters for ablating heart tissue. These approaches are attractivebecause they are minimally invasive and can be performed on a beatingheart. However, these approaches have a low success rate. The lowsuccess rate may be due to incomplete lesion formation. A fullytransmural lesion is required to ensure that the electrical impulsecausing atrial fibrillation are completely isolated from the remainderof the atrium, and this is difficult to achieve with beating heartprocedures.

Thus, the challenge for the surgeon is to place the catheter/probe alongthe correct tissue contour such that the probe makes complete contactwith the tissue. Due to the nature of the procedure and the anatomicallocations where the lesions must be created, the catheter must besufficiently flexible and adjustable such that they can match the shapeand contour of the tissue to be ablated.

Malleable and flexible cryoprobes are described in U.S. Pat. Nos.6,161,543 and 8,177,780, both to Cox, et al. The described probes have amalleable shaft. In embodiments, a malleable metal rod is coextrudedwith a polymer to form the shaft. The malleable rod permits the user toplastically deform the shaft into a desired shape so that a tip canreach the tissue to be ablated.

U.S. Pat. No. 5,108,390, issued to Potocky et al, discloses a highlyflexible cryoprobe that can be passed through a blood vessel and intothe heart without external guidance other than the blood vessel itself.

A challenge with some of the above apparatuses, however, is makingcontinuous contact along the anatomical surface such that a continuouslesion may be created. This challenge is amplified not only because ofthe varying contours and shapes of the target tissue because of thelocation in the body but also because of variations in anatomy betweenpatients. Thus, different treatment procedures and patient anatomyrequire different catheters to be designed and used. Another challengeis to be able to adjust the shape of the catheter in situ to addressthese variations in anatomy, etc.

Additional challenges with some of the above apparatuses is withefficient thermal conductivity, i.e., cooling/heat transfer, between theinternal cooling/heating elements of the devices and the exteriorjackets/sleeves of the devices. Thus, freezing and heating temperaturesmay need be efficiently transferred to the tissue to be ablated.

Accordingly, there is a need for improved methods and systems forproviding minimally invasive, adjustably shaped, safe and efficientcryogenic cooling of tissues. These improved systems include improvedapparatuses and methods to form continuous lesions in target tissueregardless of the condition being treated and variations in patientanatomy.

There is also a need for an improved apparatus and method to treat AF,atrial flutter and V-tach and to achieve more complete, durable, andsafe electrical signal isolation within the various chambers of theheart, including pulmonary vein isolation.

SUMMARY

One aspect of the embodiments of the present invention is directed to anablation apparatus for creating a lesion in target tissue, where theablation apparatus comprises an ablation shaft having a handle, a firstportion, an ablation portion, a distal tip, at least one ablation energydelivery lumen, at least one ablation energy return lumen, and a styletlumen that extends substantially along a length of the ablation shaftfrom the handle to at least the ablation portion, The ablation apparatusalso includes a stylet that is capable of being inserted into the styletlumen, where the stylet comprises a shape-memory material. In someembodiments, at least a distal portion of the stylet is pre-set with ashape that corresponds to a desired shape of the lesion to be formed.

Another aspect of the embodiments of the present invention is direct toa cryoablation catheter for creating a lesion in target tissue, wherethe cryoablation catheter comprises an ablation shaft comprising ahandle, a freezing portion, a distal tip, a plurality of cryogendelivery lumens, a plurality of cryogen return lumens, a plurality ofelectrodes on an exterior surface of the freezing portion, at least oneservice lumen, and a stylet lumen that extends substantially along alength of the ablation shaft from the handle to at least the freezingportion. The cryoablation catheter also comprises a stylet capable ofbeing inserted into the stylet lumen, where the stylet comprises ashape-memory material. In some embodiments, at least a distal portion ofthe stylet is pre-set with a shape that corresponds to a desired shapeof the lesion to be formed.

Another aspect of the embodiments of the present invention is direct toa cryoablation catheter for creating a lesion in target tissue, wherethe cryoablation catheter comprises an ablation shaft comprising ahandle, a freezing portion, a distal tip, a plurality of cryogendelivery tubes, wherein each cryogen delivery tube comprises an innertube having an outer tube surrounding the inner tube thereby defining agap between the inner tube and the outer tube, a plurality of cryogenreturn tubes, wherein each cryogen return tube comprises an inner tubehaving an outer tube surrounding the inner tube thereby defining a gapbetween the inner tube and the outer tube, a plurality of electrodes onan exterior surface of the freezing portion, at least one service lumen,and a stylet lumen that extends substantially along a length of theablation shaft from the handle to at least the freezing portion. Thecryoablation catheter also includes a stylet inserted into the styletlumen, where the stylet comprises a shape-memory material and has adistal portion that is pre-set with a shape that corresponds to adesired shape of the lesion to be formed.

An additional aspect of the embodiments of the present invention isdirected to an ablation apparatus for creating a lesion in targettissue, where the ablation apparatus comprises an ablation shaft havinga handle, a first portion, an ablation portion, a distal tip, at leastone ablation energy delivery lumen, at least one ablation energy returnlumen, and a stylet lumen that extends substantially along a length ofthe ablation shaft from the handle to at least the ablation portion, Theablation apparatus also includes a stylet that is capable of beinginserted into the stylet lumen, where the stylet comprises ashape-memory material. In some embodiments, at least a distal portion ofthe stylet is pre-set with a shape that corresponds to a desired shapeof the lesion to be formed. In some embodiments, the stylet is designedto have multiple flexibilities along its length. The multipleflexibilities are due to a removal of material in portions of the styletalong its length. The removed material can be in the form of smallerdiameter portions, circumferential grooves, longitudinal grooves and/orholes.

Another aspect of the embodiments of the present invention is direct toa cryoablation catheter for creating a lesion in target tissue, wherethe cryoablation catheter comprises an ablation shaft comprising ahandle, a freezing portion, a distal tip, a plurality of cryogendelivery lumens, a plurality of cryogen return lumens, a plurality ofelectrodes on an exterior surface of the freezing portion, at least oneservice lumen, and a stylet lumen that extends substantially along alength of the ablation shaft from the handle to at least the freezingportion. The cryoablation catheter also comprises a stylet capable ofbeing inserted into the stylet lumen, where the stylet comprises ashape-memory material. In some embodiments, at least a distal portion ofthe stylet is pre-set with a shape that corresponds to a desired shapeof the lesion to be formed. In some embodiments, the stylet is designedto have multiple flexibilities along its length. The multipleflexibilities are due to a removal of material in portions of the styletalong its length. The removed material can be in the form of smallerdiameter portions, circumferential grooves, longitudinal grooves and/orholes.

Another aspect of the embodiments of the present invention is direct toa cryoablation catheter for creating a lesion in target tissue, wherethe cryoablation catheter comprises an ablation shaft comprising ahandle, a freezing portion, a distal tip, a plurality of cryogendelivery tubes, wherein each cryogen delivery tube comprises an innertube having an outer tube surrounding the inner tube thereby defining agap between the inner tube and the outer tube, a plurality of cryogenreturn tubes, wherein each cryogen return tube comprises an inner tubehaving an outer tube surrounding the inner tube thereby defining a gapbetween the inner tube and the outer tube, a plurality of electrodes onan exterior surface of the freezing portion, at least one service lumen,and a stylet lumen that extends substantially along a length of theablation shaft from the handle to at least the freezing portion. Thecryoablation catheter also includes a stylet inserted into the styletlumen, where the stylet comprises a shape-memory material and has adistal portion that is pre-set with a shape that corresponds to adesired shape of the lesion to be formed. In some embodiments, thestylet is designed to have multiple flexibilities along its length. Themultiple flexibilities are due to a removal of material in portions ofthe stylet along its length. The removed material can be in the form ofsmaller diameter portions, circumferential grooves, longitudinal groovesand/or holes.

Additional embodiments of the present invention is directed to anablation apparatus for creating a lesion in target tissue, where theablation apparatus comprises an ablation shaft having a handle, a firstportion, an ablation portion, a distal non-ablation portion, at leastone ablation energy delivery lumen, at least one ablation energy returnlumen, and a stylet lumen that extends substantially along a length ofthe ablation shaft from the handle to at least the ablation portion. Theablation apparatus also includes a stylet capable of being inserted intothe stylet lumen where the stylet comprises a shape-memory material andhas a distal portion that is pre-set with a shape that corresponds to(i) a desired shape of the lesion to be formed and (ii) a shape of adiagnostic portion, wherein the diagnostic portion of the styletcorresponds to the distal non-ablation portion of the ablation shaft. Insome embodiments, the stylet is designed to have multiple flexibilitiesalong its length. The multiple flexibilities are due to a removal ofmaterial in portions of the stylet along its length, the alloycomposition of the stylet and the shape setting/training heat treatmentsof the stylet. The removed material can be in the form of smallerdiameter portions, circumferential grooves, longitudinal grooves and/orholes.

Another aspect of the embodiments of the present invention is directedto a cryoablation catheter for creating a lesion in target tissue wherethe cryoablation catheter comprises an ablation shaft having a handle, afreezing portion, a distal non-freezing portion, a plurality of cryogendelivery lumens, a plurality of cryogen return lumens, a plurality ofelectrodes on an exterior surface of the freezing portion, at least oneservice lumen, and a stylet lumen that extends substantially along alength of the ablation shaft from the handle to at least the freezingportion. The cryoablation catheter also includes a stylet capable ofbeing inserted into the stylet lumen, where the stylet comprises ashape-memory material. A distal portion of the cryoablation catheterincludes a diagnostic portion.

Another aspect of the embodiments of the present invention is directedto a cryoablation catheter for creating a lesion in target tissue. Thecryoablation catheter comprises an ablation shaft having a handle, afreezing portion, a distal non-freezing portion, a plurality of cryogendelivery tubes, wherein each cryogen delivery tube comprises an innertube having an outer tube surrounding the inner tube thereby defining agap between the inner tube and the outer tube, a plurality of cryogenreturn tubes, wherein each cryogen return tube comprises an inner tubehaving an outer tube surrounding the inner tube thereby defining a gapbetween the inner tube and the outer tube, a plurality of electrodes onan exterior surface of the freezing portion, at least one service lumen,and a stylet lumen that extends substantially along a length of theablation shaft from the handle to at least the freezing portion. Thecryoablation catheter also comprises a stylet inserted into the styletlumen, where the stylet comprises a shape-memory material and includes adistal portion that is pre-set with a shape that corresponds to (i) adesired shape of the lesion to be formed and (ii) a shape of adiagnostic portion to be received within a pulmonary vein entry, whereinthe diagnostic portion of the stylet corresponds to the distalnon-freezing portion of the ablation shaft.

In some embodiments, an ablation apparatus for creating a lesion intarget tissue is disclosed. The ablation apparatus comprises an ablationshaft having a handle, a first portion, an ablation portion, anon-ablation distal portion, at least one ablation energy deliverylumen, at least one ablation energy return lumen, and a stylet lumenthat extends substantially along a length of the ablation shaft from thehandle to at least the ablation portion. The ablation apparatus alsoincludes a stylet capable of being inserted into the stylet lumen wherethe stylet comprises a shape-memory material and has a distal portionthat is pre-set with a shape that corresponds to (i) a desired shape ofthe lesion to be formed and (ii) a shape of a diagnostic portion,wherein the diagnostic portion of the stylet corresponds to the distalnon-ablation portion of the ablation shaft, wherein the stylet has aplurality of flexibilities along its length, and wherein the pluralityof flexibilities are due to mechanical alterations to the stylet.

Another aspect of the present invention is directed to an ablationapparatus for creating a lesion in target where the ablation apparatuscomprises an ablation shaft having a handle, a first portion, anablation portion, a non-ablation distal portion, at least one ablationenergy delivery lumen, at least one ablation energy return lumen, and astylet lumen that extends substantially along a length of the ablationshaft from the handle to at least the ablation portion. The ablationapparatus also includes a stylet capable of being inserted into thestylet lumen, where the stylet comprises a shape-memory material and hasa distal portion that is pre-set with a shape that corresponds to (i) adesired shape of the lesion to be formed and (ii) a shape of adiagnostic portion, wherein the diagnostic portion of the styletcorresponds to the distal non-ablation portion of the ablation shaft,wherein the stylet has a plurality of flexibilities along its length,and wherein the plurality of flexibilities are due removal of materialfrom portions of the stylet.

The description, objects and advantages of embodiments of the presentinvention will become apparent from the detailed description to follow,together with the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

The above-mentioned aspects, as well as other features, aspects andadvantages of the present technology will now be described in connectionwith various embodiments, with reference to the accompanying drawings.The illustrated embodiments, however, are merely examples and are notintended to be limiting. Throughout the drawings, similar symbolstypically identify similar components, unless context dictatesotherwise. Note that the relative dimensions of the following figuresmay not be drawn to scale.

FIG. 1 illustrates a typical cryogen phase diagram;

FIG. 2 is a schematic illustration of a cryogenic cooling system;

FIG. 3 is a cryogen phase diagram corresponding to the system shown inFIG. 2 where the cryogen is N₂;

FIG. 4 provides a flow diagram that summarizes aspects of the coolingsystem of FIG. 2;

FIG. 5A is a perspective view of a cryoablation catheter, according toan embodiment of the invention;

FIG. 5B is a cross-sectional view taken along line 5B-5B of FIG. 5A;

FIG. 6 is an illustration of a cryoablation system including acryoablation catheter, according to an embodiment of the invention;

FIG. 7 is an enlarged perspective view of a distal section of thecryoablation catheter shown in FIG. 6.

FIG. 8 is a perspective view of another embodiment of a cryoablationcatheter having a flexible distal treatment section;

FIG. 9A is a cross-sectional view of an embodiment of a catheter shownin FIG. 8 taken along line 9A-9A in FIG. 9;

FIG. 9B is an enlarged view of one of the multi-layered tubes shown inFIG. 9A;

FIG. 9C is a cross sectional view of another embodiment of acryoablation catheter;

FIG. 10A is a partial sectional view of an embodiment of a cathetershown in FIG. 8;

FIG. 10B is a partial exploded view of the proximal ends of the tubeelements and the distal end of the intermediate section of an embodimentof a catheter shown in FIG. 8;

FIG. 11 is a perspective view of another embodiment of a cryoablationcatheter having a flexible distal treatment section;

FIG. 12 is an enlarged view of a portion of the distal section shown inFIG. 11;

FIG. 13 is a cross sectional view of the catheter shown in FIG. 12 takenalong line 13-13 in FIG. 12;

FIGS. 14-15 illustrate sequential deployment of the distal section ofcatheter shown in FIG. 11 from an outer sheath member;

FIG. 16 is a perspective view of another embodiment of a cryoablationcatheter having a flexible distal treatment section;

FIG. 17 is an enlarged view of the distal section of the catheter shownin FIG. 16;

FIG. 18 is a cross sectional view of the catheter shown in FIG. 17 takenalong line 17-17 in FIG. 17;

FIGS. 19A-19D show deployment of a distal section of the catheter,according to an embodiment of the invention;

FIGS. 20A-20B show reducing the diameter of the preset loop shape of thecatheter shown in FIG. 19D;

FIGS. 21A-21C show articulation of a catheter shaft, according to anembodiment of the invention;

FIGS. 22A-22B show components of an intermediate section of thecatheter;

FIG. 23A shows a perspective view of a handle for an ablation catheter,according to an embodiment of the invention;

FIG. 23B shows a partial perspective view of the handle shown in FIG.23A with the exterior removed;

FIG. 24 is a perspective view of another embodiment of a cryoablationcatheter having an internal stylet;

FIG. 25 is a cross sectional view of the catheter shown in FIG. 24 takenalong line 25-25 in FIG. 24;

FIG. 26 is an enlarged view of the multi-layered cryogen delivery/returntubes shown in FIG. 25;

FIG. 27A is a perspective view of the cryoablation catheter depicted inFIG. 24 with the internal stylet inserted;

FIG. 27B is a perspective view of the cryoablation catheter depicted inFIG. 24 with the internal stylet inserted with the flexible distalablation portion of the ablation shaft/sleeve transformed into thecurved configuration of the stylet;

FIG. 27C is a perspective view of another embodiment of a cryoablationcatheter having an internal stylet;

FIG. 28 is a cross sectional view of the catheter shown in FIG. 27Ataken along line 28-28 in FIG. 27A;

FIG. 29 depicts sample shapes for the stylet;

FIG. 30 depicts a stylet having multiple flexibilities long its length,according to an embodiment of the invention;

FIG. 31 A depicts a method of altering the flexibility of a portion of astylet, according to an embodiment of the invention;

FIG. 31 B depicts View A in FIG. 31A, according to an embodiment of theinvention;

FIG. 32A depicts a method of altering the flexibility of a portion of astylet, according to an embodiment of the invention;

FIG. 32B depicts a method of altering the flexibility of a portion of astylet, according to an embodiment of the invention;

FIG. 32C depicts a method of altering the flexibility of a portion of astylet, according to an embodiment of the invention;

FIG. 33 is an illustration of a heart, and locations of various lesionsaccording to an embodiment of the invention;

FIG. 34 is an illustration of an embodiment of endovascularcatheterization to access the heart;

FIGS. 35-36 are illustrations of a procedure to place a distal sectionof a cryoablation catheter against the endocardial wall in the leftatrium, circumscribing the left superior and inferior pulmonary veinentries, according to an embodiment of the invention;

FIGS. 37-38 are illustrations of a procedure to place a distal sectionof a cryoablation catheter against the endocardial wall in the leftatrium, circumscribing the right superior and inferior pulmonary veinentries, according to an embodiment of the invention.

FIGS. 39-40 illustrate a method for creating a box-shaped lesion,according to an embodiment of the invention, where the figures depictthe left atrium as viewed from the back of a patient;

FIG. 41 is flow diagram showing a method of creating a box-shaped lesionto enclose multiple PVs in the left atrium, according to an embodimentof the invention;

FIG. 42 is an illustration of a heart showing mitral valve electricalactivity;

FIG. 43A depicts formation of a lesion to interrupt mitral valveelectrical activity, according to an embodiment of the invention;

FIG. 43B depicts formation of a lesion to interrupt mitral valveelectrical activity, according to an embodiment of the invention;

FIG. 44 is flow diagram showing a method of creating a box-shaped lesionto enclose multiple PVs in the left atrium and a lesion to interruptmitral valve electrical activity, according to an embodiment of theinvention; and

FIG. 45 depicts formation of a lesion to interrupt electrical activityin the right atrium, according to an embodiment of the invention.

DETAILED DESCRIPTION

It is to be understood that the embodiments of the invention describedherein are not limited to particular variations set forth herein asvarious changes or modifications may be made to the embodiments of theinvention described and equivalents may be substituted without departingfrom the spirit and scope of the embodiments of the invention. As willbe apparent to those of skill in the art upon reading this disclosure,each of the individual embodiments described and illustrated herein hasdiscrete components and features that may be readily separated from orcombined with the features of any of the other several embodimentswithout departing from the scope or spirit of the embodiments of thepresent invention. In addition, many modifications may be made to adapta particular situation, material, composition of matter, process,process act(s) or step(s) to the objective(s), spirit or scope of theembodiments of the present invention. All such modifications areintended to be within the scope of the claims made herein.

Moreover, while methods may be depicted in the drawings or described inthe specification in a particular order, such methods need not beperformed in the particular order shown or in sequential order, and thatall methods need not be performed, to achieve desirable results. Othermethods that are not depicted or described can be incorporated in theexample methods and processes. For example, one or more additionalmethods can be performed before, after, simultaneously, or between anyof the described methods. Further, the methods may be rearranged orreordered in other implementations. Also, the separation of varioussystem components in the implementations described above should not beunderstood as requiring such separation in all implementations, and itshould be understood that the described components and systems cangenerally be integrated together in a single product or packaged intomultiple products. Additionally, other implementations are within thescope of this disclosure.

Conditional language, such as “can,” “could,” “might,” or “may,” unlessspecifically stated otherwise, or otherwise understood within thecontext as used, is generally intended to convey that certainembodiments include or do not include, certain features, elements,and/or steps. Thus, such conditional language is not generally intendedto imply that features, elements, and/or steps are in any way requiredfor one or more embodiments.

Conjunctive language such as the phrase “at least one of X, Y, and Z,”unless specifically stated otherwise, is otherwise understood with thecontext as used in general to convey that an item, term, etc. may beeither X, Y, or Z. Thus, such conjunctive language is not generallyintended to imply that certain embodiments require the presence of atleast one of X, at least one of Y, and at least one of Z.

Reference to a singular item, includes the possibility that there areplural of the same items present. More specifically, as used herein andin the appended claims, the singular forms “a,” “an,” “said” and “the”include plural referents unless the context clearly dictates otherwise.It is further noted that the claims may be drafted to exclude anyoptional element. As such, this statement is intended to serve asantecedent basis for use of such exclusive terminology as “solely,”“only” and the like in connection with the recitation of claim elements,or use of a “negative” limitation.

It will be understood that when an element is referred to as being“connected” or “coupled” to another element, it can be directlyconnected or coupled to the other element or intervening elements may bepresent. In contrast, if an element is referred to as being “directlyconnected” or “directly coupled” to another element, there are nointervening elements present.

It will also be understood that, although the terms first, second, etc.may be used herein to describe various elements, these elements shouldnot be limited by these terms. These terms are only used to distinguishone element from another. Thus, a first element could be termed a secondelement without departing from the teachings of the present invention.

Language of degree used herein, such as the terms “approximately,”“about,” “generally,” and “substantially,” represent a value, amount, orcharacteristic close to the stated value, amount, or characteristic thatstill performs a desired function or achieves a desired result. Forexample, the terms “approximately,” “about,” “generally,” and“substantially” may refer to an amount that is within less than or equalto 10% of, within less than or equal to 5% of, within less than or equalto 1% of, within less than or equal to 0.1% of, and within less than orequal to 0.01% of the stated amount. If the stated amount is 0 (e.g.,none, having no), the above recited ranges can be specific ranges, andnot within a particular % of the value. Additionally, numeric ranges areinclusive of the numbers defining the range, and any individual valueprovided herein can serve as an endpoint for a range that includes otherindividual values provided herein. For example, a set of values such as1, 2, 3, 8, 9, and 10 is also a disclosure of a range of numbers from1-10, from 1-8, from 3-9, and so forth.

Some embodiments have been described in connection with the accompanyingdrawings. The figures are drawn to scale, but such scale should not belimiting, since dimensions and proportions other than what are shown arecontemplated and are within the scope of the disclosed inventions.Distances, angles, etc. are merely illustrative and do not necessarilybear an exact relationship to actual dimensions and layout of thedevices illustrated. Components can be added, removed, and/orrearranged. Further, the disclosure herein of any particular feature,aspect, method, property, characteristic, quality, attribute, element,or the like in connection with various embodiments can be used in allother embodiments set forth herein. Additionally, it will be recognizedthat any methods described herein may be practiced using any devicesuitable for performing the recited steps.

While a number of embodiments and variations thereof have been describedin detail, other modifications and methods of using the same will beapparent to those of skill in the art. Accordingly, it should beunderstood that various applications, modifications, materials, andsubstitutions can be made of equivalents without departing from theunique and inventive disclosure herein or the scope of the claims.

All existing subject matter mentioned herein (e.g., publications,patents, patent applications and hardware) is incorporated by referenceherein in its entirety except insofar as the subject matter may conflictwith that of the present invention (in which case what is present hereinshall prevail).

Embodiments of the invention make use of thermodynamic processes usingcryogens that provide cooling without encountering the phenomenon ofvapor lock.

Cryogen Phase Diagram and Near Critical Point

This application uses phase diagrams to illustrate various thermodynamicprocesses. An example phase diagram is shown in FIG. 1. The phasediagram includes axes that correspond to pressure P and temperature T,and a phase line 102 that delineates the locus of all (P, T) pointswhere liquid and gas coexist. For (P, T) values to the left of the phaseline 102, the cryogen is in a liquid state, generally achieved withhigher pressures and lower temperatures, while (P, T) values to theright of the phase line 102 define regions where the cryogen is in agaseous state, generally achieved with lower pressures and highertemperatures. The phase line 102 ends abruptly in a single point knownas the critical point 104. In the case of nitrogen N₂, the criticalpoint is at P_(c)=3.396 MPa and T_(c)=−147.15° C.

When a fluid has both liquid and gas phases present during a gradualincrease in pressure, the system moves up along the liquid-gas phaseline 102. In the case of N₂, the liquid at low pressures is up to twohundred times more dense than the gas phase. A continual increase inpressure causes the density of the liquid to decrease and the density ofthe gas phase to increase, until they are equal only at the criticalpoint 104. The distinction between liquid and gas disappears at thecritical point 104. The blockage of forward flow by gas expanding aheadof the liquid cryogen (“vapor lock”) is thus avoided when a cryogenflows at conditions surrounding the critical point, defined herein as“near-critical conditions.” Factors that allow greater departure fromthe critical point while maintaining a functional flow include greaterspeed of cryogen flow, larger diameter of the flow lumen and lower heatload upon the thermal exchanger, or cryo-treatment region.

As the critical point is approached from below, the vapor phase densityincreases and the liquid phase density decreases until right at thecritical point, where the densities of these two phases are exactlyequal. Above the critical point, the distinction of liquid and vaporphases vanishes, leaving only a single, supercritical phase, where thefluid has the properties of both a liquid and a gas (i.e., a dense fluidwithout surface tension capable of frictionless flow).

Van der Waals thermodynamic equation of state is a well-establishedequation for describing gases and liquids:

(p+3/v ²)(3v−1)=8t  [Eq. 1]

where p=P/P_(c), v=V/V_(c), and t=T/T_(c), and P_(c), V_(c), and T_(c)are the critical pressure, critical molar volume, and the criticaltemperature respectively.

The variables v, p, and t are often referred to as the “reduced molarvolume,” the “reduced pressure,” and the “reduced temperature,”respectively. Hence, any two substances with the same values of p, v,and t are in the same thermodynamic state of fluid near its criticalpoint. Eq. 1 is thus referred to as embodying the “Law of CorrespondingStates.” This is described more fully in H. E. Stanley, Introduction toPhase Transitions and Critical Phenomena (Oxford Science Publications,1971), the entire disclosure of which is incorporated herein byreference in its entirety for all purposes.

In embodiments of the present invention, the reduced pressure p is fixedat a constant value of approximately one, and hence at a fixed physicalpressure near the critical pressure, while the reduced temperature tvaries with the heat load applied to the device. If the reduced pressurep is a constant set by the engineering of the system, then the reducedmolar volume v is an exact function of the reduced temperature t.

In other embodiments of the present invention, the operating pressure pmay be adjusted so that over the course of variations in the temperaturet of the device, v is maintained below some maximum value at which thevapor lock condition will result. It is generally desirable to maintainp at the lowest value at which this is true because boosting thepressure to achieve higher values of p may involve use of a more complexand more expensive compressor, resulting in more expensive procurementand maintenance of the entire apparatus support system and lower overallcooling efficiency.

The conditions for v depend in a complex way on the volume flow ratedV/dt, the heat capacity of the liquid and vapor phases, and thetransport properties such as the thermal conductivity, viscosity, etc.,in both the liquid and the vapor. The exact relationship is not derivedhere in closed form algebraically, but may be determined numerically byintegrating the model equations that describe mass and heat transportwithin the cooling device. Conceptually, vapor lock occurs when the rateof heating of the tip (or other device structure for transporting thecryogen and cooling the tissue) produces the vapor phase. The coolingpower of this vapor phase, which is proportional to the flow rate of thevapor multiplied by its heat capacity divided by its molar volume, isnot able to keep up with the rate of heating to the tip. When thisoccurs, more and more of the vapor phase is formed in order to absorbthe excess heat through the conversion of the liquid phase to vapor inthe cryogen flow. This creates a runaway condition where the liquidconverts into vapor phase to fill the tip, and effectively all cryogenflow stops due to the large pressure that results in this vapor phase asthe heat flow into the tip increases its temperature and pressurerapidly. This condition is called “vapor lock.”

In accordance with one embodiment of the present invention, the liquidand vapor phases are substantially identical in their molar volume. Thecooling power is at the critical point, and the cooling system avoidsvapor lock. Additionally, at conditions slightly below the criticalpoint, the apparatus may avoid vapor lock as well.

Cryoablation System

FIG. 2 provides a schematic illustration of a structural arrangement fora cryogenic system in one embodiment, and FIG. 3 provides a phasediagram that illustrates a thermodynamic path taken by the cryogen whenthe system of FIG. 2 is operated. The circled numerical identifiers inthe two figures correspond so that a physical position is indicated inFIG. 2 where operating points identified along the thermodynamic pathare achieved. The following description thus sometimes makessimultaneous reference to both the structural drawing of FIG. 2 and tothe phase diagram of FIG. 3 in describing physical and thermodynamicaspects of the cooling flow.

For purposes of illustration, both FIGS. 2 and 3 make specific referenceto a nitrogen cryogen, but this is not intended to be limiting.Embodiments of the invention may more generally be used with anysuitable cryogen such as, for example, argon, neon, helium, hydrogen,and oxygen.

In FIG. 3, the liquid-gas phase line is identified with reference label256 and the thermodynamic path followed by the cryogen is identifiedwith reference label 258.

A cryogenic generator 246 is used to supply the cryogen at a pressurethat exceeds the critical-point pressure P_(c) for the cryogen at itsoutlet, referenced in FIGS. 2 and 3 by label {circle around (1)}. Thecooling cycle may generally begin at any point in the phase diagramhaving a pressure above or slightly below P_(c), although it isadvantageous for the pressure to be near the critical-point pressureP_(c). The cooling efficiency of the process described herein isgenerally greater when the initial pressure is near the critical-pointpressure P_(c) so that at higher pressures there may be increased energyrequirements to achieve the desired flow. Thus, embodiments maysometimes incorporate various higher upper boundary pressure butgenerally begin near the critical point, such as between 0.8 and 1.2times P_(c), and in one embodiment at about 0.85 times P_(c).

As used herein, the term “near critical” is meant to refer to near theliquid-vapor critical point. Use of this term is equivalent to “near acritical point” and it is the region where the liquid-vapor system isadequately close to the critical point, where the dynamic viscosity ofthe fluid is close to that of a normal gas and much less than that ofthe liquid; yet, at the same time its density is close to that of anormal liquid state. The thermal capacity of the near critical fluid iseven greater than that of its liquid phase. The combination of gas-likeviscosity, liquid-like density and very large thermal capacity makes ita very efficient cooling agent. Reference to a near critical pointrefers to the region where the liquid-vapor system is adequately closeto the critical point so that the fluctuations of the liquid and vaporphases are large enough to create a large enhancement of the heatcapacity over its background value. The near critical temperature is atemperature within ±10% of the critical point temperature. The nearcritical pressure is between 0.8 and 1.2 times the critical pointpressure.

Referring again to FIG. 2, the cryogen is flowed through a tube, atleast part of which is surrounded by a reservoir 240 of the cryogen in aliquid state, reducing its temperature without substantially changingits pressure. In FIG. 2, reservoir is shown as liquid N₂, with a heatexchanger 242 provided within the reservoir 240 to extract heat from theflowing cryogen. Outside the reservoir 240, thermal insulation may beprovided around the tube to prevent unwanted warming of the cryogen asit is flowed from the cryogen generator 246. At point {circle around(2)}, after being cooled by being brought into thermal contact with theliquid cryogen, the cryogen has a lower temperature but is atsubstantially the initial pressure. In some instances, there may be apressure change, as is indicated in FIG. 3 in the form of a slightpressure decrease, provided that the pressure does not dropsubstantially below the critical-point pressure P_(c), i.e. does notdrop below the determined minimum pressure. In the example shown in FIG.3, the temperature drop as a result of flowing through the liquidcryogen is about 50° C.

The cryogen is then provided to a device for use in cryogenicapplications. In the exemplary embodiment shown in FIG. 2, the cryogenis provided to an inlet 236 of a catheter 224, such as may be used inmedical cryogenic endovascular applications, but this is not arequirement.

Indeed, the form of the medical device may vary widely and includewithout limitation: instruments, appliances, catheters, devices, tools,apparatus', and probes regardless of whether such probe is short andrigid, or long and flexible, and regardless of whether it is intendedfor open, minimal, non-invasive, manual or robotic surgeries.

In embodiments, the cryogen may be introduced through a proximal portionof a catheter, continue along a flexible intermediate section of thecatheter, and into the distal treatment section of the catheter. As thecryogen is transported through the catheter, and across the cryoablationtreatment region 228, between labels {circle around (2)} and {circlearound (3)} in FIGS. 2 and 3, there may be a slight change in pressureand/or temperature of the cryogen as it moves through the interface withthe device, e.g. cryoablation region 228 in FIG. 2. Such changes maytypically show a slight increase in temperature and a slight decrease inpressure. Provided the cryogen pressure remains above the determinedminimum pressure (and associated conditions), slight increases intemperature do not significantly affect performance because the cryogensimply moves back towards the critical point without encountering theliquid-gas phase line 256, thereby avoiding vapor lock.

Flow of the cryogen from the cryogen generator 246 through the catheter224 or other device may be controlled in the illustrated embodiment withan assembly that includes a check valve 216, a flow impedance, and/or aflow controller. The catheter 224 itself may comprise a vacuuminsulation 232 (e.g., a cover or jacket) along its length and may have acold cryoablation region 228 that is used for the cryogenicapplications. Unlike a Joule-Thomson probe, where the pressure of theworking cryogen changes significantly at the probe tip, theseembodiments of the invention provide relatively little change inpressure throughout the apparatus. Thus, at point {circle around (4)},the temperature of the cryogen has increased approximately to ambienttemperature, but the pressure remains elevated. By maintaining thepressure above or near the critical-point pressure P_(c) as the cryogenis transported through the catheter, vapor lock are avoided.

The cryogen pressure returns to ambient pressure at point {circle around(5)}. The cryogen may then be vented through vent 204 at substantiallyambient conditions.

Examples of cryoablation systems, their components, and variousarrangements are described in the following commonly-assigned U.S.patents and U.S. patent applications: U.S. patent application Ser. No.10/757,768, which issued as U.S. Pat. No. 7,410,484, on Aug. 12, 2008entitled “CRYOTHERAPY PROBE,” filed Jan. 14, 2004 by Peter J. Littrup etal.; U.S. patent application Ser. No. 10/757,769, which issued as U.S.Pat. No. 7,083,612 on Aug. 1, 2006, entitled “CRYOTHERAPY SYSTEM,” filedJan. 14, 2004 by Peter J. Littrup et al.; U.S. patent application Ser.No. 10/952,531, which issued as U.S. Pat. No. 7,273,479 on Sep. 25, 2007entitled “METHODS AND SYSTEMS FOR CRYOGENIC COOLING,” filed Sep. 27,2004 by Peter J. Littrup et al.; U.S. patent application Ser. No.11/447,356, which issued as U.S. Pat. No. 7,507,233 on Mar. 24, 2009entitled “CRYOTHERAPY SYSTEM,” filed Jun. 6, 2006 by Peter Littrup etal.; U.S. patent application Ser. No. 11/846,226, which issued as U.S.Pat. No. 7,921,657 on Apr. 12, 2011 entitled “METHODS AND SYSTEMS FORCRYOGENIC COOLING,” filed Aug. 28, 2007 by Peter Littrup et al.; U.S.patent application Ser. No. 12/018,403, which issued as U.S. Pat. No.8,591,503 on Nov. 26, 2013 entitled “CRYOTHERAPY PROBE,” filed Jan. 23,2008 by Peter Littrup et al.; U.S. patent application Ser. No.13/046,274, which issued as U.S. Pat. No. 8,387,402 on Mar. 5, 2013entitled “METHODS AND SYSTEMS FOR CRYOGENIC COOLING,” filed Mar. 11,2011 by Peter Littrup et al.; U.S. patent application Ser. No.14/087,947, which is pending entitled “CRYOTHERAPY PROBE,” filed Nov.22, 2013 by Peter Littrup et al.; U.S. patent application Ser. No.12/744,001, which issued as U.S. Pat. No. 8,740,891, on Jun. 3, 2014entitled “FLEXIBLE MULTI-TUBULAR CRYOPROBE,” filed Jul. 29, 2010 byAlexei Babkin et al.; U.S. patent application Ser. No. 12/744,033, whichissued as U.S. Pat. No. 8,740,892, on Jun. 3, 2014 entitled “EXPANDABLEMULTI-TUBULAR CRYOPROBE,” filed Jul. 29, 2010 by Alexei Babkin et al.and U.S. patent application Ser. No. 14/915, 632 entitled “ENDOVASCULARNEAR CRITICAL FLUID BASED CRYOABLATION CATHETER AND RELATED METHODS,”filed Sep. 22, 2014 by Alexei Babkin, et al., the contents of each ofthe above-identified U.S. patents/applications are incorporated hereinby reference in their entireties for all purposes.

A method for cooling a target tissue in which the cryogen follows athermodynamic path similar to that shown in FIG. 3 is illustrated withthe flow diagram of FIG. 4. At block 310, the cryogen is generated witha pressure that exceeds the critical-point pressure and is near thecritical-point temperature. The temperature of the generated cryogen islowered at block 314 through heat exchange with a substance having alower temperature. In some instances, this may conveniently be performedby using heat exchange with an ambient-pressure liquid state of thecryogen, although the heat exchange may be performed under otherconditions in different embodiments. For example, a different cryogenmight be used in some embodiments, such as by providing heat exchangewith liquid nitrogen when the working fluid is argon. Also, in otheralternative embodiments, heat exchange may be performed with a cryogenthat is at a pressure that differs from ambient pressure, such as byproviding the cryogen at lower pressure to create a colder ambient.

The further cooled cryogen is provided at block 318 to acryogenic-application device, which may be used for a coolingapplication at block 322. The cooling application may comprise chillingand/or freezing, depending on whether an object is frozen with thecooling application. The temperature of the cryogen is increased as aresult of the cryogen application, and the heated cryogen is flowed to acontrol console at block 326. While there may be some variation, thecryogen pressure is generally maintained greater than the critical-pointpressure throughout blocks 310-326; the principal change inthermodynamic properties of the cryogen at these stages is itstemperature. At block 330, the pressure of the heated cryogen is thenallowed to drop to ambient pressure so that the cryogen may be vented,or recycled, at block 334. In other embodiments, the remainingpressurized cryogen at block 326 may also return along a path to block310 to recycle rather than vent the cryogen at ambient pressure.

Cryoablation Catheters

Embodiments of the cryoablation apparatus of the present invention mayhave a wide variety of configurations. For example, one embodiment ofthe present invention is a flexible catheter 400 as shown in FIG. 5A.The catheter 400 includes a proximally disposed housing or connector 410adapted to fluidly connect to a fluid source (not shown).

A plurality of fluid transfer tubes 420 are shown extending from theconnector 410. These tubes include a set of inlet fluid transfer tubes422 for receiving the inlet flow from the connector and a set of outletfluid transfer tubes 424 for discharging flow from the connector 410.

In embodiments each of the fluid transfer tubes is formed of materialthat maintains flexibility in a full range of temperatures from −200° C.to ambient temperature. In embodiments, the fluid transfer tubes 420 areformed of annealed stainless steel or a polymer such as polyimide. Insuch configurations, the material may maintain flexibility at nearcritical temperature. In embodiments, each fluid transfer tube has aninside diameter in a range of between about 0.1 mm and 1 mm (preferablybetween about 0.2 mm and 0.5 mm). Each fluid transfer tube may have awall thickness in a range of between about 0.01 mm and 0.3 mm(preferably between about 0.02 mm and 0.1 mm).

An end cap 440 is positioned at the ends of the fluid transfer tubes toprovide fluid transfer from the inlet fluid transfer tubes to the outletfluid transfer tubes. The endcap 440 is shown having an atraumatic tip.The endcap 440 may be any suitable element for providing fluid transferfrom the inlet fluid transfer tubes to the outlet fluid transfer tubes.For example, endcap 440 may define an internal chamber, cavity, orpassage serving to fluidly connect tubes 422,424.

With reference to FIG. 5B, an outer sheath 430 is shown surrounding thetube bundle 420. The outer sheath serves to hold the tubes in a tubulararrangement, and protect the construct from being penetrated ordisrupted by foreign objects and obstacles.

A temperature sensor 432 is shown on the surface of the distal section.Temperature sensor may be a thermocouple to sense a temperaturecorresponding to the adjacent tissue, and sends the signal back througha wire in the tube bundle to the console for processing. Temperaturesensor may be placed elsewhere along the shaft or within one or more ofthe fluid transport tubes to determine a temperature difference betweeninflow and outflow.

There are many configurations for tube arrangements. In embodiments thefluid transfer tubes are formed of a circular array, wherein the set ofinlet fluid transfer tubes comprises at least one inlet fluid transfertube 422 defining a central region of a circle and wherein the set ofoutlet fluid transfer tubes 424 comprises a plurality of outlet fluidtransfer tubes spaced about the central region in a circular pattern. Inthe configuration shown in FIG. 5B, the fluid transfer tubes 422,424fall within this class of embodiments.

During operation, the cryogen/cryogenic fluid arrives at the catheterthrough a supply line from a suitable cryogen source at a temperatureclose to −200° C. The cryogen is circulated through the multi-tubularfreezing zone provided by the exposed fluid transfer tubes, and returnsto the connector. Cryogen flows into the freeze zone through the inletfluid transfer tube 422 and flows out of the freeze zone through theoutlet fluid transfer tubes 424.

In embodiments, the nitrogen flow does not form gaseous bubbles insidethe small diameter tubes under any heat load, so as not to create avapor lock that limits the flow and the cooling power. By operating atthe near critical condition for at least an initial period of energyapplication, the vapor lock is eliminated as the distinction between theliquid and gaseous phases disappears. After initially operating undernear critical conditions, e.g., for nitrogen, at a temperature near thecritical temperature of −147.15° C. and a pressure near the criticalpressure of 3.396 MPa, the operating pressure may be decreased as isdisclosed and described in commonly assigned U.S. patent applicationSer. No. 14/919,681 entitled “PRESSURE MODULATED CRYOABLATION SYSTEM ANDRELATED METHODS,” filed Oct. 21, 2015 by Alexei Babkin, the contents ofwhich are incorporated herein by reference in their entirety for allpurposes.

A multi-tube design may be preferably to a single-tube design becausethe additional tubes can provide a substantial increase in the heatexchange area between the cryogen and tissue. Depending on the number oftubes used, cryo-instruments can increase the contact area several timesover previous designs having similarly sized diameters with singleshafts/tubes. However, embodiments of the invention are not intended tobe limited to a single or multi-tubular design except where specificallyrecited in the appended claims.

Cryoablation Console

FIG. 6 illustrates a cryoablation system 950 having a cart or console960 and a cryoablation catheter 900 detachably connected to the consolevia a flexible elongate tube 910. The cryoablation catheter 900, whichshall be described in more detail below in connection with FIG. 7,contains one or more fluid transport tubes to remove heat from thetissue.

The console 960 may include or house a variety of components (not shown)such as, for example, a generator, controller, tank, valve, pump, etc. Acomputer 970 and display 980 are shown in FIG. 6 positioned on top ofcart for convenient user operation. Computer may include a controller,timer, or communicate with an external controller to drive components ofthe cryoablation systems such as a pump, valve or generator. Inputdevices such as a mouse 972 and a keyboard 974 may be provided to allowthe user to input data and control the cryoablation devices.

In embodiments computer 970 is configured or programmed to controlcryogen flowrate, pressure, and temperatures as described herein. Targetvalues and real time measurement may be sent to, and shown, on thedisplay 980.

FIG. 7 shows an enlarged view of distal section of cryoablationapparatus 900. The distal section 900 is similar to designs describedabove except that treatment region 914 includes a flexible protectivecover 924. The cover serves to contain leaks of the cryogen in the eventone of the fluid transport tubes is breached. Although a leak is notexpected or anticipated in any of the fluid delivery transport tubes,the protective cover provides an extra or redundant barrier that thecryogen would have to penetrate in order to escape the catheter during aprocedure. In embodiments the protective cover may be formed of metal.

Additionally, a thermally conducting liquid may be disposed withinspaces or gaps between the transport tubes and the inner surface of thecover to enhance the device's thermal cooling efficiency duringtreatment. In embodiments the thermally conductive liquid is water.

Cover 924 is shown being tubular or cylindrically shaped and terminatesat distal tip 912. As described herein, the cooling region 914 containsa plurality of fluid delivery and fluid return tubes to transport acooling fluid through the treatment region 914 causing heat to betransferred/removed from the target tissue. In embodiments, the cryogenis transported through the tube bundle under physical conditions nearthe fluid's critical point in the phase diagram. The cover serves to,amongst other things, contain the cooling fluid and prevent it fromescaping from the catheter in the event a leak forms in one of thedelivery tubes.

Although a cover is shown in FIGS. 6-7, the invention is not intended tobe so limited except as where recited in the appended claims. Theapparatus may be provided with or without a protective cover and used tocool a target tissue.

Tube within Tube

FIG. 8 shows a partial view of a cryoablation catheter 1010 according toanother embodiment of the invention having a protective means tomitigate leaks in the event a cooling fluid/cryogen escapes from thecryogen delivery tubes described above. In particular, catheter 1010comprises a plurality or bundle 1012 of flexible multi-layer cryoenergytransfer tubes, each of which comprises two tubes in a coaxialarrangement, namely a tube within a tube.

FIG. 9A shows a cross-sectional view taken along line 9A-9A of FIG. 8.The bundle 1012 of multilayer tubes is shown with the fluid deliverytubes 1014 and the fluid return tubes 1015 assembled in a parallelarrangement. The tube bundle 1012 is shown having 12 tubes/linesincluding four (4) fluid return tubes 1015 a-1015 d and eight (8) fluiddelivery tubes 1014 a-1014 h. The fluid delivery tubes 1014 a-1014 hform a perimeter around the fluid return tubes 1015 a-1015 d. Thisarrangement ensures that colder delivery fluid/cryogen is adjacent tothe tissue to be ablated/frozen and warmer return fluid/cryogen isshielded from the tissue to be ablated/frozen.

FIG. 9B shows an enlarged cross-sectional view of fluid delivery tube1014 d of FIG. 9A. The first or inner tube 1013 is shown coaxiallysurrounded by a second or outer tube 1018. A space or gap 1020 betweenthe exterior surface of the inner tube 1013 and the interior surface ofthe outer tube 1018 is capable of being filled with a thermallyconductive media 1021 as described herein. In embodiments, the gap 1020has an annular shape. All of the fluid delivery tubes 1014 as well asthe fluid return tubes 1015 can have a similar tube within a tubeconstruction.

In the event of a leak of the cooling fluid 1016 or breach of the innertube 1013 during use, the cooling fluid 1016 is contained within the gap1020 between the inner tube 1013 and the outer tube 1018. This tubewithin a tube feature adds an additional safety element to the device asany leaking fluid/cryogen 1016 is contained within the catheter and isprevented from entering the patient. In some embodiments, a pressuresensor/device or gauge may be incorporated to monitor the pressure ofthe thermally conductive media 1021 in the gap 1020. Therefore, iffluid/cryogen 1016 breaches the inner tube 1013 and leaks into the gap1020, the pressure in the gap 1020 and hence, the conductive media 1021will increase. Should a change in pressure occur above a thresholdlimit, the system can be programmed to halt ablation thereby preventingpotential harm to a patient and/or notify the user/physician of thischange in pressure.

The inner tube 1013 may be fabricated and made from materials asdescribed herein in connection with other flexible tubes fortransporting the cooling fluid.

The outer tube 1018 material should also be flexible to enable elasticdeflection of the distal treatment section to allow the distal treatmentsection to transform its shape as disclosed herein. In some embodiments,the outer tube is not inflatable, distensible nor expandable such thatits size and shape remains substantially unaffected by the presence ofthe thermally conductive media 1021 contained therein. Non-limitingexemplary materials for the outer tube 1018 include polymers and metalsor alloys. An example of an outer tube 1018 material is Nitinol orpolyimide.

The number of tubes forming the tubular bundle 1012 may vary widely. Insome embodiments, the tubular bundle 1012 includes 5-15 tubes, and morepreferably, includes between 8-12 tubes comprising fluid delivery tubes1014 and fluid return tubes 1015.

The cross-sectional profile of the tube bundle 1012 may also vary.Although FIG. 9A shows a substantially circular profile, in embodiments,the profile may be rectangular, square, cross or t-shaped, annular orcircumferential, or another shape profile, including some of thearrangements described above. The tubes may also be braided, woven,twisted, or otherwise intertwined together, as depicted in FIGS. 9, 14and 16 of commonly assigned U.S. patent application Ser. No. 14/915,632entitled “ENDOVASCULAR NEAR CRITICAL FLUID BASED CRYOABLATION CATHETERAND RELATED METHODS,” filed Sep. 22, 2014 by Alexei Babkin, et al., theentire contents of which are incorporated herein by reference for allpurposes.

The diameter of the freezing section or tubular bundle may vary. Inembodiments, the diameter of the bundle ranges from about 1-3 mm, and ispreferably about 2 mm.

FIG. 9C shows a cross-section of a cryoablation catheter having anothertubular arrangement 1017. The eight (8) tubular elements (1019 a-1019 dand 1023 a-1023 d) are spaced or distributed circumferentially about acore element 1025. Preferably, as shown, fluid delivery elements/tubes(1019 a-1019 d) and fluid return elements/tubes (1023 a-1023 d)alternate along the circumference of the catheter.

Each inner tubular element (e.g., 1019 a) includes an outer tubularelement (e.g., 1027 a) coaxially surrounding the inner tubular elementthereby creating a space or gap which can be filled with a thermallyconductive media/fluid as described with respect to FIG. 9B.

Steering elements, sensors and other functional elements may beincorporated into the catheter. In embodiments, steering elements areincorporated into a mechanical core such as the mechanical core 1025shown in FIG. 9C.

FIG. 10A shows an enlarged cut-away view of the catheter at detail 10Ain FIG. 8, illustrating tube bundle 1012 fluidly connected to the endportion 1040 of an intermediate section of the catheter 1010.

FIG. 10B shows an exploded view of a proximal section of the tube bundle1012 and the intermediate section of catheter 1040. Tube bundle 1012,having inner tubular elements 1013 a-1013 d extending beyond outertubular elements/covers 1018 a-1018 d of fluid delivery lines 1014, canbe inserted into intermediate section of catheter 1040.

With reference to FIGS. 10A-10B, fluid delivery lines 1014 are shownbundled together and inserted/joined to main line 1032. An adhesive plug1042 or seal, gasket, or stopper, etc. may be applied to facilitate andensure a fluid seal between the tube members. The cooling power fluid(CPF) is transported to the fluid delivery lines 1014 from the fluiddelivery main line 1032.

The proximal ends of outer tubular elements/covers 1018 a-d, which areoffset from proximal ends of inner tubular elements 1013 a-d, are showninserted into intermediate section 1040 of catheter such that thethermally conductive fluid (TCF) within lumen 1050 can fill gaps 1020(FIG. 9B) of each of the multi-layer cryoenergy tubular elements. Anadhesive plug 1044 (weld or bond) may be applied to facilitate a fluidtight and robust connection. Press fits, heat, and other fabricationtechniques can be applied to join components as is known to those ofskill in the art.

FIG. 11 shows another cryoablation catheter 500 including a distaltreatment section 510, a handle 520, and an umbilical cord 530. Theproximal end of the umbilical cord 530 terminates in connector 540,which is inserted into receptacle port 560 on console 550.

One or more ancillary connector lines 570 are shown extending proximallyfrom the handle 520. The tubular lines 570 may serve to provide variousfunctionality including without limitation (a) flushing; (b) vacuum; (c)thermally conductive liquid described above; and/or (d) temperature andpressure sensor conductors.

The catheter 500 is also shown having electrical connector 580 extendingproximally from the handle 520. Electrical connector 580 may be coupledto an EP recording system for analyzing electrical information detectedin the distal treatment section 510. Examples of systems for analyzingthe electrical activity include, without limitation, the GE HealthcareCardioLab II EP Recording System, manufactured by GE Healthcare, USA andthe LabSystem PRO EP Recording System manufactured by Boston ScientificInc. (Marlborough, Mass.). The recorded electrical activity may also beused to evaluate or verify the continuous contact with the target tissueas described in commonly assigned International Patent Application No.PCT/US16/51954, entitled “TISSUE CONTACT VERIFICATION SYSTEM”, filedSep. 15, 2016 by Alexei Babkin, et al., the entire contents of which areincorporated herein by reference for all purposes.

FIG. 12 shows an enlarged view of a portion of the distal section 510 ofthe catheter 500. Ring-shaped electrodes 602, 604 are circumferentiallydisposed about shaft 606. Although two electrodes are shown, more orless electrodes may be present on the shaft for sensing electricalactivity. In embodiments, up to 12 electrodes are provided on the shaft.In one embodiment, 8 electrodes are axially spaced along the shaft 606.

FIG. 13 is a cross section of the catheter shown in FIG. 12 taken alongline 13-13. The catheter shaft is shown having a mechanical core 620extending along the central axis, and a plurality of energy deliveringtube constructs 630 extending parallel and circumferentially disposedabout the mechanical core.

Each tube construct 630 is shown having dual layers as described abovein connection with FIGS. 8-9 and a thermally conductive liquid layerdisposed there between.

A tubular line 624 is shown for housing conducting wires 626 for thevarious sensors described herein.

The mechanical core 620 may be constructed to provide a preset shape tothe catheter distal treatment section. With reference to FIG. 13, themechanical core includes a metal tubular member 622 having a presetshape. The preset shape matches the target anatomy to make continuouscontact with the target anatomy. An exemplary material for the presettubular element 622 is Nitinol. FIG. 13 also shows an exterior layer orcover concentrically surrounding the Nitinol tube. The exterior covermay be a flexible polymer such as, for example, PET. Collectively, theinner PET layer 620 and outer shaft layer 606 form a fluidly-sealedannular chamber to house the plurality of tubular constructs 630.

With reference to FIGS. 14-15, a catheter 608 is shown being deployedfrom an outer sheath 642. Initially, catheter distal section 606 isdisposed within a lumen of external sheath 642, and prohibited fromassuming its preset shape. The distal section 606 and external sheath642 are moved axially relative to one another. For example, the cathetermay be ejected from the sheath. Once the catheter is free fromconstraint, it assumes the preset shape as shown in FIG. 15.

Mechanical core assembly biases the shape of the catheter distal section608, forcing the energy delivering elements into a curvilinear shape. Inembodiments, the catheter shape is adapted to create lesions in theright atrium useful in treating atrial flutter. The shape shown in FIG.15, for example, is a single loop or elliptical shape which hascurvature to match target zones of tissue in the right atrium useful intreating atrial flutter. Additional apparatus and methods for treatingatrial flutter are described in commonly assigned U.S. PatentApplication No. 61/981,110, filed Apr. 17, 2014, now InternationalPatent Application No. PCT/US2015/024778, filed Oct. 21, 2015 entitled“ENDOVASCULAR NEAR CRITICAL FLUID BASED CRYOABLATION CATHETER HAVINGPLURALITY OF PREFORMED TREATMENT SHAPES,” the contents of both of whichare incorporated herein by reference in their entireties for allpurposes.

FIG. 16 shows another cryoablation catheter 700 including a distaltreatment section 710, a handle 720, and an umbilical cord 730 whichterminates in connector 740. Similar to the system described above inconnection with FIG. 11, connector 740 may be inserted into a receptacleport on a console.

Additional lines 742, 744 are shown extending proximally from handle.Lines 742, 744 provide various functionalities to the distal treatmentsection 710 during a procedure. Example functionalities include, withoutlimitation, temperature, EP recording, pressure, fluid flush, sourceliquids, etc.

FIG. 17 is an enlarged view of the catheter distal section followingdeployment. The treatment section is shown having a generally looped orelliptical shape 714. An intermediate section 716 is shown providing abend or articulation from central axis 718. Such functionality aids inpositioning the treatment section in continuous direct contact with thetissue. In embodiments, the shape is configured to create complete PVIin the left atrium.

FIG. 18 is an enlarged cross sectional view of a portion of the distaltreatment section. The catheter shaft is shown having a mechanical core750 extending along the central axis, and a plurality of energydelivering tube constructs 752 extending parallel and circumferentiallyabout the mechanical core. One or more spare tubular elements 754,758can be incorporated into the perimeter space in combination with energydelivery elements. Tubular element 754 holds a plurality of electricalconductors to transmit electrical activity from sensors or ringelectrodes 756 present on the distal treatment section. Tubular element758 may provide vacuum or liquid to the catheter for various functionsdescribed herein.

Mechanical core 750 is shown extending axially through the treatmentsection and comprising a plurality of members 760, 762 which extendthrough the distal treatment section to bias the distal section into apreset shape such as the loop shape shown in FIG. 17. In particular, inembodiments, the mechanical core can include a biased shape element 760such as a Nitinol wire, and an axially movable control member 762connected to a distal tip of the treatment section to adjust thecurvature of the preset shape. Core may include additional lumens766,768 if desired. The mechanical core acts to shape the distaltreatment section to a first preset loop shape, and can be furtheradjusted by the control member to make continuous contact with a targettissue surface.

FIGS. 19A-19D illustrate sequentially deployment of an ablation catheter810 from a first arcuate shape having a slight bend to a secondconfiguration having a complete ring or circular shape 820. The shape isassumed once the catheter treatment section is not constrained by theouter sheath 812.

FIGS. 20A-20B show an enlarged view of the catheter 800 of FIG. 19Dexcept that the loop has been adjusted by reducing its diameter Φ₁. Asdescribed herein, a control member extending through the shaft of thedistal treatment section is pulled to reduce the diameter of the presetloop Φ₁ to diameter Φ₂ as shown in FIG. 20A. FIG. 20B shows the loopadjusted to an even smaller diameter Φ₃ than that shown in FIG. 20A.

The diameter Φ of the loop may vary. In embodiments, the diameter of theloop is controlled to range from 2 cm to 5 cm, and in embodiments,preferably about 2-3 cm.

FIGS. 21A-21C show sequentially articulation of the intermediate section814 of the catheter. The intermediate section 814 is shown having anouter support or reinforcing structure 816. In embodiments, the supportlayer 816 is a spring or coil.

FIG. 21A shows catheter intermediate section 814 substantially straightor aligned with the shaft axis.

FIG. 21B shows catheter intermediate section having a slightarticulation forming angle θ₁with shaft axis.

FIG. 21C shows catheter intermediate section having further articulationθ₂ with shaft axis. The degree of articulation may vary and be adjustedby the physician as described below. In embodiments, the degree ofarticulation is up to 120 degrees from the central shaft axis, and morepreferably up to about 90 degrees.

FIGS. 22A-22B show examples of components/structures for articulatingthe intermediate section. The components include a coil 832, second pullwire 834, and spine 836. The pull wire 834 is fixed to a distal locationof the intermediate section. Pulling on the pull wire results indeflecting or articulating the coil 832. Spine 836 is showndiametrically opposite the pull wire. The spine serves to bias thedirection that the catheter bends when the pull wire is retracted andserves to return the catheter to its straightened position when the pullwire is released. In particular, when the pull wire is retracted, thecatheter bends towards the pull wire along a plane including the pullwire, central coil axis, and the spine.

The various articulating components/structures may be made of a widevariety of materials. Exemplary materials include without limitationNitinol, stainless steel, or other materials having the functionalitydescribed herein. Additionally, the components may be fabricated fromwire, tubular elements, or sheets of stock material. In one embodiment,the coil and spring are integrally formed from a sheet of metal alloy.The desired shape may be machined or laser cut to create the spine andrib elements, allowing for biased articulation. See also US PatentPublication No. 2003/0195605, filed May 30, 2003, entitled “CryogenicCatheter with Deflectable Tip” to Kovalcheck et al. for further detailsdescribing catheters comprising a spring, pull wire and spine forcontrolling deflection.

FIG. 23A shows a perspective view of a handle 852 of an ablationcatheter. A flexible catheter shaft 854 extends from a distal section856 of the handle. Umbilical cord 858 and various other functional linesand connectors 859 are shown extending proximally from a proximalsection 860 of handle.

Handle 852 is shown having an ergonomic design including a smooth gentlycurved intermediate section 862 that allows a user to conveniently holdthe handle.

Handle is shown comprising a knob 864 which may be rotated relative tothe handle body to control the diameter of the deployed loop asdescribed above. An axially movable hub 866 is shown proximal to theknob. Movement of the hub 866 forward or backwards serves to adjust orarticulate the deployed shaft as described above. Additionally, handlemay be rotated as a whole to steer the catheter in one direction oranother. Collectively, the handle provides a convenient and semiautomatic apparatus to turn, articulate, and control the diameter orsize of the deployed structure.

FIG. 23B shows a partial perspective view of the handle shown in FIG.23A with the exterior removed for clarity. A segment of an externalthread or teeth 872 are shown. The teeth 872 mate with grooves or threadin the knob 864. The teeth are linked to a first control memberdescribed above for changing the shape or diameter of the loop. As theknob is rotated, the pull wire is moved simultaneously.

Slider 874 is also shown in handle. Slider 874 is joined to hub 866 suchthat movement of the hub causes the slider to move. Slider is alsolinked to a second control member as described above for articulatingthe catheter shaft. When the exterior hub is moved by the physician, thesecond control member articulates the shaft.

Although the handle is shown having a knob, hub, and slider, theinvention is not intended to be so limited. The invention can includeother levers, gears, buttons, and means for causing the above describedfunctionality.

Depicted in FIG. 24 is an ablation catheter 880 according to anotherembodiment of the invention. In this embodiment, the ablation catheter880 comprises two main components—(a) an ablation shaft/sleeve 881 fordelivering ablation energy to a site of interest within the human bodyand (b) a stylet 882 that is capable of being inserted into an internalhollow cavity within the ablation shaft/sleeve 881. As will be discussedin more detail below, at least a portion of the ablation shaft/sleeve881 is made of a flexible material such that this portion of theablation shaft/sleeve 881 can assume a shape of the stylet 882 that isinserted therein and that is constructed from a shape memory alloy.While the ablation catheter 880 will be described herein for use as acryoablation catheter that creates lesions by freezing tissue with anysuitable cryogen (for example, and not limited to, nitrogen, argon,neon, helium, hydrogen, and oxygen), in other embodiments, the ablationcatheter can be used with other ablation energies such as, for example,radiofrequency, microwave, laser, and high frequency ultrasound (HIFU).

As depicted in FIG. 24, the ablation shaft/sleeve 881 includes a handleportion (not shown and which may be constructed in accordance with anyof the handle embodiments disclosed herein), a first shaft portion 883,a flexible shaft portion 884, a flexible distal ablation portion 885 anda distal ablation tip 886. In some embodiments, the ablation catheter880 may also include a plurality of electrodes 887 on the flexibledistal ablation portion 885 that may be used to detect electricalactivity in the target tissue in order to evaluate or verify continuouscontact of the flexible distal ablation portion 885 with the targettissue as described in commonly assigned International PatentApplication No. PCT/US16/51954, entitled “TISSUE CONTACT VERIFICATIONSYSTEM”, filed Sep. 15, 2016 by Alexei Babkin, et al., the entirecontents of which are incorporated herein by reference for all purposes.In some embodiments, electrodes 887 may be included on the distalablation tip 886. In some embodiments, the first shaft portion 883 maybe flexible, semi-flexible, semi-rigid or rigid. In some embodiments,the first shaft portion 883 is less flexible than the flexible shaftportion 884, however, the first shaft portion 883 will still be flexiblesuch that it can be delivered through the venous system of the body tothe target tissue.

In some embodiments, the ablation shaft/sleeve 881 may comprise a handleportion, a flexible shaft portion 884, a flexible distal ablationportion 885 and a distal ablation tip 886. That is, the ablationshaft/sleeve 881 may be flexible along its entire length,

FIG. 25 depicts a cross-sectional view of the ablation catheter 881taken along line 25-25 in FIG. 24 with the stylet 882 not being insertedinto the ablation shaft/sleeve 881. As can be seen in thecross-sectional view, the ablation shaft/sleeve 881 includes a pluralityof multilayer cryogen delivery tubes/lumens 888 for transporting thecryogen to the flexible distal ablation portion 885 and a plurality ofmultilayer cryogen return tubes/lumens 889 for transporting the cryogenaway from the flexible distal ablation portion 885. Also shown are aplurality of service tubes/lumens 885 that may include catheter controlwires, electrode wires 892, or any other elements that may be desired.The plurality of multilayer cryogen delivery tubes/lumens 888, theplurality of multilayer cryogen return tubes/lumens 889 and theplurality of service tubes/lumens 885 are arranged in a circular arrayaround a hollow tube/lumen 890 that is adapted to receive the stylet 882therein. The hollow tube/lumen 890 extends along the length of theablation shaft/sleeve 881 from the handle to at least the flexibledistal ablation portion 885.

While FIG. 25 depicts four (4) multilayer cryogen delivery tubes 888,four (4) multilayer cryogen return tubes 889 and four (4) servicetubes/lumens 891, the embodiments of the invention are not intended tobe so limited and may include any number of multilayer cryogen deliverytubes 888, multilayer cryogen return tubes 889 and service tubes/lumens891 depending on the desired ablating power of the catheter or thecondition that the catheter will be used to treat. Additionally, whileFIG. 25 depicts a certain configuration of the multilayer cryogendelivery tubes 888, the multilayer cryogen return tubes 889 and theservice tubes/lumens 891, specifically that pairs of multilayer cryogendelivery tubes 888 and multilayer cryogen return tubes 889 are locatedadjacent to one another and separated with a service tubes/lumens 891,the embodiments of the invention are not intended to be so limited andmay include any number of different configurations for the multilayercryogen delivery tubes 888, the multilayer cryogen return tubes 889 andthe service channels/tubes 891.

FIG. 26 shows an enlarged cross-sectional view of the multilayer cryogendelivery tubes 888 and multilayer cryogen return tubes 889 of FIG. 25.The first or inner tube 893 is shown coaxially surrounded by a second orouter tube 894. The lumen 895 of the inner tube 893 is designed toreceive the flow of cryogen. The inner tube 893 and outer tube 894 arearranged such that a space or gap 896 is created between the exteriorsurface of the inner tube 893 and the interior surface of the outer tube894. This gap 896 is capable of being filled with a thermally conductivemedia 897 as described herein. In some embodiments, the gap 896 has anannular shape. All of the multilayer cryogen delivery tubes 888 as wellas the multilayer cryogen return tubes 889 can have a similar tubewithin a tube construction.

In the event of a leak of the cryogen flowing through lumen 895 orbreach of the inner tube 893 during use, the leaking cryogen iscontained within the gap 896 between the inner tube 893 and the outertube 894. This tube within a tube construction adds an additional safetyelement to the device as any leaking fluid/cryogen is contained withinthe catheter and is prevented from entering the patient. In someembodiments, a pressure sensor/device or gauge may be incorporated tomonitor the pressure of the thermally conductive media 897 in the gap896. Therefore, if fluid/cryogen breaches the inner tube 893 and leaksinto the gap 896, the pressure in the gap 896 and hence, the pressure ofthe conductive media 897 will increase. Should a change in pressureoccur above a threshold limit, the system can be programmed to (a) haltablation thereby preventing potential harm to a patient and/or (b)notify the surgeon of this change in pressure.

The inner tubes 893 may be fabricated and made from materials asdescribed herein in connection with other flexible tubes fortransporting the cryogen/cooling fluid. The outer tubes 895 may also bemanufactured from a flexible material to enable elastic deflection ofthe flexible shaft portion 884 and the flexible distal ablation portion885 of the ablation shaft/sleeve 881 to allow these portions totransform their shapes to assume the shape of the stylet 882 asdisclosed herein. In some embodiments, the outer tube 895 is notinflatable, distensible nor expandable such that its size and shaperemains substantially unaffected by the presence of the thermallyconductive media 897 contained therein. Non-limiting exemplary materialsfor the outer tube 895 include polymers and metals or alloys. An exampleof an outer tube 894 material is polyimide.

The diameter of the flexible distal ablation portion 885 may vary. Insome embodiments, the diameter of the flexible distal ablation portion885 ranges from about 1-3 mm, and is preferably about 2 mm.

FIG. 27A and FIG. 27B depict an embodiment of the ablation catheter 880with the stylet 882 fully inserted into the ablation shaft/sleeve 881where FIG. 27A depicts the ablation catheter 880 with the stylet 882inserted therein prior to the distal portion 898 of the stylet 882transforming into its pre-set shape and FIG. 27B shows the ablationcatheter 880 transformed into a pre-set shape of the distal portion 898of the inserted stylet 882. FIG. 28 shows a cross-sectional view of theablation catheter 880 of FIG. 27 taken along line 28-28 in FIG. 27A. Ascan be seen in FIG. 28, the stylet 882 is inserted into the hollowtube/lumen 890 of the ablation shaft/sleeve 881.

In some embodiments, in order to improve insertability/sliding of thestylet 882 within the hollow tube/lumen 890 of the ablation shaft/sleeve881, the distal tip of the stylet 882 can be designed to have tipgeometries that are tapered, that have a smaller diameter than thedistal portion 898 of the stylet 882, are rounded, etc.

Depicted in FIG. 29 are sample shapes that can be pre-set into thedistal portion 898 of the stylet 882. In some embodiments, the length ofthe distal portion 898 corresponds to at least a portion of the lengthof the flexible distal ablation portion 885 of the ablation shaft/sleeve881. Thus, when the stylet 882 is in place in the hollow tube/lumen 890of the ablation shaft/sleeve 881 and the flexible distal ablationportion 885 is positioned at the ablation site within the patient, thedistal portion 898 of the stylet 882 transforms into its pre-set shapecausing the flexible distal ablation portion 885 to transform to acorresponding shape as depicted in FIG. 27B.

FIG. 27C depicts another embodiment of the ablation catheter 880 withthe stylet 882 fully inserted into the ablation shaft/sleeve 881. Inthis embodiment, instead of the flexible distal ablation portion 885including a distal ablation tip, the flexible distal ablation portion885 includes a non-ablating/non-freezing diagnostic portion 2000 that isused to position and/or hold the flexible distal ablation portion 885 inplace against the target tissue to be ablated. Because the diagnosticportion 2000 is designed to be non-ablative, the ablation shaft/sleeve881 portion that corresponds to the diagnostic portion 2000 does notinclude multilayer cryogen delivery tubes/lumens 888 and multilayercryogen return tubes/lumens 889. In some embodiments, the diagnosticportion 2000 includes a plurality of electrodes 887.

The shape of the non-ablating diagnostic portion 2000 is pre-set in theshape memory alloy of the stylet 882. In the embodiment depicted in FIG.27C, the diagnostic portion 2000 has a coiled spiral shape that isdesigned to be received within the pulmonary vein entries in the heart.Thus, when used to treat atrial fibrillation, the flexible distalablation portion 885 is inserted into the left atrium. After the shapetransforms into the shape depicted in FIG. 27C, the flexible distalablation portion 885 is maneuvered adjacent to one of the pulmonary veinentries and the diagnostic portion 2000 is inserted into the pulmonaryvein entry until the flexible distal ablation portion 885 contacts thetissue surrounding the pulmonary vein entry thereby encircling thepulmonary vein entry. Thus, the diagnostic portion 2000 ensures that theflexible distal ablation portion 885 is properly positioned around thepulmonary vein entry, that it will be held in place around the pulmonaryvein entry and that a lesion will be formed completely around thepulmonary vein entry. As will be readily understood by those of skill inthe art, the diagnostic portion 2000 can be designed to have any shapebased on the area/tissue within the body to be ablated by the flexibledistal ablation portion 885. That is, the diagnostic portion 2000 can bedesigned to have any shape that aids in properly and accuratelypositioning and/or holding the flexible distal ablation portion 885 inplace in contact with the target tissue to be ablated.

The shape of the distal portion 898 of the stylet 882 can be based onthe type of procedure/treatment that the ablation catheter 880 will beused to perform as well as the patient's anatomy where the treatment isbeing performed. Thus, if a procedure is performed with one stylet 882having a specific shape/orientation and the ablation was not successfulbecause of incomplete lesion formation, for example, the surgeon cansimply remove the stylet 882 from the ablation shaft/sleeve 881 whileleaving the ablation shaft/sleeve 881 in place in the patient. Thesurgeon can then (a) choose a different stylet 882 having a distalportion 898 with a different size and/or shape than that of thepreviously-used stylet 898, (b) insert this new stylet 882 into thehollow tube/lumen 890 of the ablation shaft/sleeve 881 and (c) continuewith the ablation procedure. The surgeon can do this as many times as isnecessary to achieve a successful ablation, e.g., complete lesionformation.

In some embodiments, a portion 899 of the stylet 882 can be set with apre-determined articulation angle, which can be helpful in directing theflexible distal ablation portion 885 into contact with the target tissuefor the ablation. In some embodiments, the articulation portion 899 ofthe stylet 882 corresponds to the flexible shaft portion 884 of theablation shaft/sleeve 881.

In some embodiments, the stylet 882 can be designed to have differentflexibilities along its length. As depicted in FIG. 30, in oneembodiment, the stylet 882 can be designed to have three (3) portionsidentified as portions “A,” “B” and “C” with different flexibilities.For example, portion “A” can have a first flexibility, portion “B” canhave a second flexibility and portion “C” can have a third flexibility.In some embodiments, portion “B” is more flexible that portions “A” and“C” as it may be necessary for portion “B” and its associated portion ofthe ablation shaft/sleeve 881 to articulate such that portion “A” andits associated portion of the ablation shaft/sleeve 881 can bemanipulated into contact with the target tissue within the heart to beablated. It may be necessary for portions “A” and “C” and theirassociated portions of the ablation shaft/sleeve 881 to be lessflexible/more rigid or stiffer than portion “B” such that pressure/forcecan be applied during delivery of the ablation shaft/sleeve 881 andtransferred to the flexible distal ablation portion 885 of the ablationshaft/sleeve 881 such that the flexible distal ablation portion 885 canbe manipulated into the proper position against the target tissue andheld in place.

In some embodiments, portions of the stylet 882 can be designed to havea flexibility similar to the flexibility of corresponding portions ofthe of the ablation shaft/sleeve 881. In some embodiments, the ablationshaft/sleeve 881 can be designed to have a uniform flexibility, however,the flexibility of specific portions the ablation shaft/sleeve 881 canbe adjusted or controlled based on the flexibility of correspondingportions of the stylet 882. Thus, the stylet 882 may be responsible forcontrolling the flexibility of the catheter 880.

The flexibility along the length of the stylet 882 can be changed oraltered in various ways. For example, in some embodiments, theproperties of the shape memory material from which the stylet 882 isconstructed, can be altered. One property that can be altered is thetransition temperature of the shape memory alloy. Thus, a shape memoryalloy that may have a certain flexibility at one temperature can have adifferent flexibility at the same temperature due to an alteredtransition temperature.

As depicted in FIG. 31A and FIG. 31B, in one embodiment, the flexibilityalong the length of the stylet 882 can be altered by changing thediameter of the stylet 882. FIG. 31B, which is a detail of View A inFIG. 31A, shows that material can be removed from stylet 882 such thatportions of the stylet 882 have a diameter “d1” while other portions ofthe stylet 882 have a diameter “d2,” which is less than diameter “d1.”Thus, portions of the stylet 882 that have either diameters thatalternate between “d1” and “d2” or that have extended lengths “L2” witha diameter “d2,” are more flexible than portions of the stylet 882 thathave a consistent diameter “d1.” In some embodiments, the flexibilitycan be altered based on lengths “L1” and “L2” of the larger diameterportions “d1” and smaller diameter portions “d2,” respectively. Thus,portions of the stylet 882 having lengths “L2” of smaller diameterportions “d2” that are greater in length than the length “L1” of largerdiameter portions “d1” will be more flexible than portions of the stylet882 having lengths “L2” of smaller diameter portions “d2” that areshorter in length than the length “L1” of larger diameter portions “d1.”In other embodiments, any number of different diameter stylet portions,i.e., “d1,” “d2,” “d3,” “d4,” etc., of any lengths may be designed toimpart the desired flexibility on the stylet 882 and these differentdiameter stylet portions may be arranged in any order and/orconfiguration to impart the desired flexibility on the stylet 882.

In some embodiments, as depicted in FIGS. 32A-32C, the flexibility ofportions of the stylet 882 can be altered with the inclusion of aplurality of circumferential grooves 5000, a plurality of longitudinalgrooves 5010, or a plurality of holes 5020. In the embodiment depictedin FIG. 32A, the flexibility of the stylet 882 can be altered based onthe width “W1” of the circumferential grooves 5000, the spacing “S1”between adjacent groves 5000 and the spacing “L2” between adjacent sets5030 of circumferential grooves 5000. Thus, (a) embodiments havingcircumferential grooves 5000 that have a width “W1” that is greater thana width “W1” of circumferential grooves 5000 in other embodiments, (b)embodiments having circumferential grooves 5000 that have a closerspacing “S1” between adjacent grooves 5000 than spacing “S1” betweencircumferential grooves 5000 in other embodiments and (c) embodimentshaving sets 5030 of circumferential grooves 5000 that have a shorterdistance “L2” between adjacent sets 5030 of circumferential grooves 5000than in other embodiments, will be more flexible than in the otherembodiments. Various combinations of widths “W1”, spacings “S1” anddistances “L2” can be designed to achieve the desired flexibilities ofdifferent portions of the stylet 882.

In the embodiment depicted in FIG. 32B, the flexibility of the stylet882 can be altered based on the width “W2” of the longitudinal grooves5010, the spacing “S1” between adjacent grooves 5010, the spacing “L2”between adjacent sets 5040 of longitudinal grooves 5010 and the length“L3” of the longitudinal grooves 5010. Thus, (a) embodiments havinglongitudinal grooves 5010 that have a width “W2” that is greater than awidth “W2” of longitudinal grooves 5010 in other embodiments (b)embodiments having longitudinal grooves 5010 that have a length “L3”that is greater than a length “L3” of longitudinal grooves 5010 in otherembodiments, (c) embodiments having longitudinal grooves 5010 that havea closer spacing “S1” between adjacent longitudinal grooves 5010 thanspacing “S1” between adjacent longitudinal grooves 5010 in otherembodiments and (d) embodiments having sets 5040 of longitudinal grooves5010 that have a shorter distance “L2” between adjacent sets 5040 oflongitudinal grooves 5010 than in other embodiments, will be moreflexible than in the other embodiments. Various combinations of widths“W2”, lengths “L3,” spacings “S1” and distances “L2” can be designed toachieve the desired flexibilities of different portions of the stylet882.

In the embodiment depicted in FIG. 32C, the flexibility of the stylet882 can be altered based on the diameter “D3” of the holes 5020, thespacing “S1” between adjacent holes 5020 in the X-direction, the spacing“S2” between adjacent holes 5020 in the Y-direction and the spacing “L2”between adjacent sets 5050 of holes 5020. Thus, (a) embodiments havingholes 5020 that have a diameter “D3” that is greater than a diameter“D3” of holes 5020 in other embodiments, (b) embodiments having holes5020 that have a closer spacing “S1” between adjacent holes 5020 in theX-direction than spacing “S1” between adjacent holes 5020 in theX-direction in other embodiments, (c) embodiments having holes 5020 thathave a closer spacing “S2” between adjacent holes 5020 in theY-direction than spacing “S2” between adjacent holes 5020 in theY-direction in other embodiments and (d) embodiments having sets 5050 ofholes 5020 that have a shorter distance “L2” between adjacent sets 5050of holes 5020 than in other embodiments, will be more flexible than inthe other embodiments. Various combinations of diameters “D3”, spacings“S1,” spacings “S2” and distances “L2” can be designed to achieve thedesired flexibilities of different portions of the stylet 882.

In most embodiments, the degree of flexibility correlates to the amountof stylet material that is removed or that remains in the portions ofthe stylet 882 where altered flexibilities are desired. Portions of thestylet 882 having more material removed will be more flexible thanportions of the stylet 882 having less material removed.

In the stylet embodiments disclosed herein, combinations of alterationsmay be used. For example, desired flexibilities can be achieved bycombining smaller diameter portions with circumferential grooves 5000and/or longitudinal grooves 5010 and/or holes 5020.

The multiple flexibilities in the embodiments disclosed herein are dueto a removal of material in portions of the stylet along its length. Theremoved material can be in the form of smaller diameter portions,circumferential grooves, longitudinal grooves and/or holes and any othershapes as will be readily apparent to those skilled in the art.

In some embodiments, multiple flexibilities along the length of thestylet 882 can be achieved by altering/changing the alloy composition ofthe shape memory alloy material used to construct certain portions ofthe stylet 882. In some embodiments, the multiple flexibilities of thestylet 882 can be achieved based on different shape setting heattreatments at different locations along the length of the stylet 882.

In some embodiments, the ablation catheter 880 may be packaged as a kitwith multiple stylets 882 having various shapes and sizes thereby givingthe physician different options regarding the size and shape of thelesions to be created during the ablation procedure. These kits can betreatment specific. Therefore, only stylets having shapes and sizes forthe specific procedure can be included in the kits. Thus, the ablationcatheter 880 of this embodiment allows a single, universal ablationshaft/sleeve 881 to be designed and constructed that can be used for amultitude of various ablation procedures based only on providing stylets882 specific for the procedure being performed. Constructing a single,universal ablation shaft/sleeve 881 is more cost efficient and providesfor higher production rates than having to construct multiple ablationcatheters that are designed to have different shapes and differenthandle functionality.

In some embodiments, the ablation shaft/sleeve 881 can be used toperform ablations without a stylet 882 inserted therein.

As previously disclosed, in some embodiments, the stylet 882 can madefrom a shape memory alloy such as, for example, nickel titanium(Nitinol). The shape of the stylet can be set with varying degrees ofshape setting/training heat treatments (temperature, time, the amount ofprior cold work, Bend and Free Recovery (“BFR”) testing, which determinethe shape memory alloy's final mechanical properties, austenite finish(“Af”) transformation temperature, and alloy composition.

In some experiments with embodiments of a cryoablation catheter, asfreezing of the ablation catheter 880 begins, expansion of the stylet882 distal portion 898 and hence, expansion of the distal ablationportion 885 was noticed. This expansion prevented the loop of the distalablation portion 885 from completely encircling/enclosing causingnon-continuous lesions to form around the respective anatomicalfeatures. Through experimentation and characterization of severaltemperatures, times, quench settings, and BFR testing, it was determinedthat the Af temperatures of the nitinol stylet 882 needed to be set tobelow freezing temperatures (0° C.) in order for ice to form around thecatheter distal portion thereby locking the shape of the distal ablationportion 885 before the distal ablation portion 885 had an opportunity toexpand. It was also determined that expansion of the distal ablationportion 885 could be controlled by setting the Af temperature asexpansion increases with Af temperature. Although this expansion wasoriginally viewed as a disadvantage, it was determined that acryoablation catheter with both expanding and non-expanding capabilitiescould be advantageous when ablating various parts of the anatomy.

In some embodiments, a stylet 882 is formed using Nitinol wire for itsunique properties of shape memory and superelasticity. The successfuljoining of the stylet 882 in combination with the flexible properties ofthe ablation shaft/sleeve 881 requires precise control of the stylet's882 transformational and mechanical properties. Transformational andmechanical properties of the stylet 882 are imparted through heattreatment settings and BFR testing. During the shaping process, activeAf temperature specifications are locked into the material by processtemperature, time, and quench settings. Temperatures above the active Aftemperatures such as ambient and body temperatures, keep the nitinolwire of the stylet 882 in a super elastic and austenitic state, whilethe material is in the twinned martensitic phase at temperatures belowthe active Af temperature and is therefore, easily deformed. Thispre-programmed Af temperature controls the amount of movement orexpansion of the shaped distal portion 898 of the stylet 882 as itundergoes phase transformation into the martensitic phase. Due to theflexibility of the ablation catheter distal ablation portion 885, amethod was developed to “pre-program” in Af temperatures to control andmanipulate expansion of the distal ablation portion's 885 shape for allanatomical structures resulting in improved efficacy.

As the stylet 882 is advanced into the ablation shaft/sleeve 881, ittransforms the distal ablation portion 885 of the ablation shaft/sleeve881 into the shape of the pre-set shape of the distal portion 898 of thestylet 882 as it is heated to body temperature (approximately 37° C.).As cryogen is delivered into the ablation shaft/sleeve 881, freezingbegins in the distal section while temperatures drop from bodytemperature down to cryogenic temperatures, which in some embodiments,is approximately −196° C. Ice formation around the distal ablationportion 885 of the ablation shaft/sleeve 881 occurs near the freezingtemperature of water (approximately 0° C.). The Af temperature of thedistal portion 898 of the stylet 882 determines if either (i) movementor expansion will occur before ice formation on the distal ablationportion 885 of the ablation shaft/sleeve 881 because the Af temperaturesare set above the freezing temperature or (ii) no movement or expansionwill occur because the Af temperatures are set below the freezingtemperature. Expansion/movement of the distal ablation portion 885 ofthe ablation shaft/sleeve 881 is increased as the Af temperature isincreased in the distal portion 898 of the stylet 882. Thesepre-programmed Af temperatures can therefore either prevent the distalablation portion 885 of the ablation shaft/sleeve 881 from expanding orcause the distal ablation portion 885 of the ablation shaft/sleeve 881to expand incrementally, based on the Af temperature of the distalportion 898 of the stylet 882.

Furthermore, both expanding and non-expanding options for the distalablation portion 885 of the ablation shaft/sleeve 881 are significant tothe efficacy of the ablation as anatomical structures contain severalmechanical properties including stiffness, elasticity, hardness, andlubricity while expanding/contracting with the vital functions of thebody.

As will be discussed in more detail below, in use, the ablationshaft/sleeve 881 is delivered to an area of interest with the body, insome embodiments, for example, the left atrium of the heart to treatatrial fibrillation or the right atrium to treat atrial flutter or theright and left ventricles to treat ventricular tachycardia, through adelivery catheter. After the ablation shaft/sleeve 881 is in positionand depending on the ablation treatment being performed and thepatient's anatomy, the surgeon chooses a stylet 881 to use. The surgeonthen inserts this stylet 881 through the catheter handle and into thehollow tube/lumen 890 of the ablation shaft/sleeve 881 until the distalportion 898 of the stylet 882 is in place within the flexible distalablation portion 885. Once in place, the shape memory characteristics ofthe distal portion 898 of the stylet 882 cause the distal portion 898 totransform into its pre-set shape thereby causing the flexible distalablation portion 885 to transform into a corresponding shape. Thesurgeon can then proceed with the ablation treatment.

Applications

Embodiments of the cryoablation apparatus (catheters, probes, etc.)described herein have a wide range of diagnostic and therapeuticapplications including, for example, endovascular-based cardiac ablationand more particularly, the endovascular-based cardiac ablation treatmentof atrial fibrillation.

FIG. 33 shows examples of target ablation lesions in a pulmonary veinisolation (PVI) procedure for the treatment of atrial fibrillation.

The basic structures of the heart 1 are shown in FIG. 33 including theright atrium 2, the left atrium 3, the right ventricle 4 and the leftventricle 5. The vessels include the aorta 6 (accessed through thefemoral artery), the superior vena cava 6 a (accessed through thesubclavian veins) and the inferior vena cava 6 b (accessed through thefemoral vein).

Exemplary target lesions for a PVI procedure include lesion 8 whichsurrounds and isolates all left pulmonary veins (PVs), and lesion 9which surrounds and isolates all right pulmonary veins (PVs). Asdescribed further herein, the invention may include application orcreation of additional lesions to increase the effectiveness of thetreatment. Also, it is to be understood that although the followingdiscussion primarily focuses on embodiments for performing PVI, thetechnology and procedure described herein for producing these lesionscan be used to create other lesions in an around the heart and otherorgans such as that described in international patent application nos.PCT/US2012/047484 to Cox et al. and PCT/US2012/047487 to Cox et al.corresponding to International Publication Nos. WO 2013/013098 and WO2013/013099 respectively, the contents of each of which is herebyincorporated by reference in their entirety.

FIG. 34 illustrates one technique to reach the left atrium with thedistal treatment section of a catheter. The procedure may be performedunder conscious sedation, or general anesthetic if desired.

A peripheral vein (such as the femoral vein FV) is punctured with aneedle. The puncture wound is dilated with a dilator to a sizesufficient to accommodate an introducer sheath, and an introducer sheathwith at least one hemostatic valve is seated within the dilated puncturewound while maintaining relative hemostasis.

With the introducer sheath in place, the guiding catheter 10 or sheathis introduced through the hemostatic valve of the introducer sheath andis advanced along the peripheral vein, into the target heart region(e.g., the vena cavae, and into the right atrium 2). Fluoroscopicimaging can be used to guide the catheter to the selected site.

Once in the right atrium 2, the distal tip of the guiding catheter ispositioned against the fossa ovalis in the intraatrial septal wall. Aneedle or trocar is then advanced distally through the guide catheteruntil it punctures the fossa ovalis. A separate dilator may also beadvanced with the needle through the fossa ovalis to prepare an accessport through the septum for seating the guiding catheter. The guidingcatheter thereafter replaces the needle across the septum and is seatedin the left atrium through the fossa ovalis, thereby providing accessfor devices through its own inner lumen and into the left atrium.

Placement of the above tools may be carried out with guidance from oneor more of the following: fluoroscopy, intracardiac pressures,transesophageal echocardiography (TEE), and intracardiacechocardiography (ICE).

FIGS. 35-38 illustrate a method for deploying a ring-shaped catheter inthe left atrium and around pulmonary vein entries for treating variousheart conditions such as atrial fibrillation.

With reference first to FIG. 35, a cross sectional view of the heartincludes the right atrium RA 2, left atrium LA 3, left superiorpulmonary vein LSPV entry, and left inferior pulmonary vein LIPV entry.Guide catheter 2100 is shown extending through the septum and into theleft atrium.

Though not shown, mapping catheters may be positioned in the entry tothe LSPV of the left atrium for monitoring electrical signals of theheart. The mapping catheters may be placed in other locations, such as,for example the coronary sinus (CS). Examples of mapping cathetersinclude the WEBSTER® CS Bi-Directional Catheter and the LASSO® Catheter,both of which are manufactured by Biosense Webster Inc. (Diamond Bar,Calif. 91765, USA). Another example of mapping and cryo-treatment systemis described in US Patent Publication No. 2015/0018809 to Mihalik.

Optionally, an esophageal warming balloon may be placed in the esophagusto mitigate collateral damage arising from creating the lesions. Anesophageal warming balloon prevents the cold temperatures from reachingthe inner layer of cells of the esophagus, and can prevent formation of,e.g., an atrio-esophageal fistula. An example of a suitable esophagealwarming balloon apparatus that may be used is described in commonlyassigned U.S. patent application Ser. No. 15/028,927, entitled“ENDOESOPHAGEAL BALLOON CATHETER, SYSTEM, AND RELATED METHOD,” filedOct. 12, 2014 by Alexei Babkin, et al., the contents of which isincorporated herein by reference in its entirety for all purposes.

FIG. 36 illustrates a distal section of the cryoablation catheter 2116advanced through the guide sheath 2100. The energy element 2118 is shownhaving a circular shape formed as disclosed and described herein andurged against the endocardium. As described herein the shape may beadjusted to make continuous contact with the tissue, and to form anelliptical or circular-shaped continuous lesion (such as lesion 8 shownin FIG. 33) which encloses all the left PV entries.

In embodiments the shape is modified by reducing the diameter of loop,articulating the intermediate section of the shaft, and rotating orsteering the catheter distal section. Collectively, the steps ofdeployment, diameter control, steering and articulation can place theentire circumference of the loop in continuous contact with theendocardium tissue. When energy is applied to the distal treatmentsection such as, for example, by flowing a cryogen through the distaltreatment section, a continuous elongate ring-shaped lesion (frozentissue) is formed such as the lesion 8 shown in FIG. 33, enclosing allleft pulmonary vein entries.

FIG. 37 illustrates formation of a ring-shaped lesion around the rightsuperior pulmonary vein (RSPV) entries and the right inferior pulmonaryvein (RIPV) entries such as, for example, lesion 9 shown in FIG. 33. Incontrast to the somewhat linear (straight shot) positioning shown inFIGS. 35-36, the catheter neck region 2116 shown in FIG. 37 is deflectednearly 180 degrees to aim towards the right pulmonary veins. Energyelement portion 2118 is positioned around the RSPV and RIPV entries.

FIG. 37 shows the energy element 2118 deployed in a circular shape andcontacting the endocardium. As described herein the shape may beadjusted to make better contact with the tissue in order to form anelongate ring-shaped, continuous lesion that engulfs or surrounds theRSPV and RIPV entries.

A similar elongate ring-shaped, continuous lesion can be formed tosurround the left superior pulmonary vein (LSPV) entries and the leftinferior pulmonary vein (LIPV) entries.

FIG. 38 shows the catheter 2116 deflected to aim towards the posteriorwall of the left atrium. Energy element portion 2118 is manipulated toform a loop and urged against the posterior wall, overlapping withpreviously-formed right and left lesions.

Optionally, and not shown, guidewires can be advanced from the guidesheath and used to navigate the catheter treatment section intoposition.

The shape of the lesion and pattern may vary. In embodiments, and withreference to FIG. 39, a “box-shaped” lesion 900 is shown surroundingmultiple pulmonary vein entries in a PVI procedure. The box-shapedlesion surrounds the pulmonary vein entries on both the left and rightsides of the left atrium.

The box-shaped lesion 900 may be formed in various ways. In someembodiments, the box-shaped lesion is formed by overlapping acombination of lesions, which can have similar or different shapes(e.g., oval, ellipse, ring, etc.) to form an overall larger continuouslesion, which may have a box-like shape 900 as shown in FIG. 39.

With reference to the illustration shown in FIG. 40, and thecorresponding flow diagram shown in FIG. 41, a method 1000 for forming abox-shaped lesion in the left atrium that encircles/encloses allpulmonary vein (RSPV, RIPV, LSPV and LIPV) entries, is described.

Step 1010 states to advance the cryoablation catheter into the leftatrium, which can be performed using a guide sheath, for example.

Step 1020 states to navigate the treatment section (energy elementportion 2118) of the catheter to one side of the left atrium and intothe antrum of the superior and inferior pulmonary veins on that side ofthe atrium.

Step 1030 states to manipulate the treatment section (energy elementportion 2118) of the catheter to form a loop-like shape and to adjustthe size of the loop to make full circumference tissue contact withtissue to enclose the superior and inferior vein entries on that side ofthe atrium.

Step 1040 states to verify tissue contact. This step may be performedusing, for example, electrodes mounted on the distal treatment sectionas disclosed and escribed in commonly assigned International PatentApplication No. PCT/US16/51954, entitled “TISSUE CONTACT VERIFICATIONSYSTEM”, filed Sep. 15, 2016 by Alexei Babkin, et al., the entirecontents of which are incorporated herein by reference for all purposes.The tissue electrocardiograms (ECGs) may be displayed using an EPrecording system.

Optionally, an esophageal balloon (EBB) (as discussed above) is advancedinto the esophagus in the vicinity of the heart. The EBB is inflated anda thermally conducting liquid is circulated through the balloon for theduration of the ablation treatment. As described herein, the EEBminimizes collateral damage to tissue adjacent the ablation zone bywarming the tissue during the ablation cycle.

Step 1050 states to perform the ablation by freezing the tissue tocreate a first continuous lesion enclosing/surrounding the pulmonaryvein entries on the first side of the left atrium, for example, the leftside lesion 901 in FIG. 40. The duration of the tissue freeze may be upto 3 minutes or more, and generally ranges from about 1 to 3 minutes,and preferable is about 2 minutes. In embodiments, the freeze stepcomprises a single application of uninterrupted ablation energy.

In some embodiments, the duration of the energy application ranges fromapproximately 10 to 60 seconds, and sometimes is less than or equal toapproximately 30 seconds.

The duration of the freeze cycle may vary. A physician or electrophysiologist can elect to terminate the freeze cycle as desired (e.g.,before or after the anticipated time period has passed). Examples ofreasons for early termination include: a desire to reposition thecatheter, a desire to improve catheter-tissue contact, or a safetyconcern.

Step 1060 states to confirm ablation is complete. Electrical activityfrom the electrodes on the distal treatment section may be monitored.During freezing, the electrocardiograms (ECG) will present abnormalsignals due to freezing of the tissue and blood in contact with thefreezing tip. After freezing is completed, however, the ECGs should notshow any signal or evidence of a voltage potential in the tissue due totissue necrosis.

If, however, the ECG signals/signatures reappear after the freezing stepindicating that there is still electrical activity in the tissue, thisis evidence that the ablation was not complete and that PVI may not havebeen achieved. In the event PVI was not achieved, the above describedapplicable steps can be repeated.

In some embodiments, another freeze in the same location can becommenced. Or, the catheter may be repositioned or otherwise adjusted tomake better contact with the target tissue. Then, an additional freezemay be performed.

Performing an additional freeze can be beneficial especially if thedistance between the pulmonary veins is unusually large. When thedistance between the pulmonary veins is unusually large, isolating thepulmonary vein entries with only one continuous lesion is a challenge.In a sub population of patients with unusually enlarged hearts, formingan additional lesion around the pulmonary vein entries increases thelikelihood of a complete and durable PVI.

Additionally, in some situations, it may be desirable to narrow theablation loop to accommodate a single vein. In embodiments, the methodcomprises performing a single vein isolation around the ostium of thesingle vein. The diameter of the catheter loop is reduced from therelatively large size for isolating multiple veins to the applicablesize of the single vein. In embodiments, the single vein isolation isperformed subsequent to the larger multiple vein isolations.

Step 1070 states to repeat the applicable steps for the pulmonary veinson the other side of the left atrium. That is, for example, after theleft vein antrum is isolated, the catheter loop will be navigated to theright vein antrum and all relevant steps should be repeated to create asecond, right side lesion (e.g., lesion 902 of FIG. 40).

Step 1080 states to repeat the applicable above described steps for theposterior wall lesion (lesion 903 in FIG. 40). Once both the LSPV andLIPV antrum and the RSPV and RIPV vein antrum are isolated, the loopedtreatment section of the catheter is navigated to the posterior wall ofthe left atrium.

Optionally, the EBB is inflated in the esophagus and activated prior toablation of the posterior wall. The other applicable steps for placingthe left and right lesions are repeated for the posterior lesion. Theposterior lesion 903 is more centrally located, and shown in FIG. 40overlapping the left and right antrum lesions (901 and 902,respectively). Lesion 903 is also shown extending from the floor to theceiling of the left atrium.

Although the method describes a particular order to create the leftpulmonary vein, right pulmonary vein and posterior wall lesions,embodiments of the invention are not intended to be so limited exceptwhere specifically recited in the appended claims. The order that thelesions are created may vary. For example, in embodiments, the rightside or posterior lesion may be performed prior to the left side lesion.

As can be seen in FIGS. 39 and 40, collectively, the plurality ofindependent lesions (901, 902, 903) form a composite box-like shapedcontinuous lesion 900 (FIG. 39) that encloses all the pulmonary veinentries on all sides (left, right, top and bottom) of the left atrium.In embodiments, the sum of the sub-lesions form an enclosure in theshape of a box, square, or rectangle. Performing the ablations to formthis composite, continuous lesion 900 effectively electrically isolatesall the pulmonary vein entries in the left atrium.

In patients that have atrial flutter in addition to paroxysmal atrialfibrillation and in patients that have non-paroxysmal atrialfibrillation, in addition to forming the lesions (901, 902, 903)discussed above with reference to FIGS. 39-41, it will be necessary toform an additional lesion to isolate the mitral valve. In thesepatients, as depicted in FIG. 42, there is electrical activity/current950 that flows around the mitral valve 960. Therefore, the flow of thiselectrical activity/current 950, must be interrupted andstopped/prevented in order to treat these patients. Depicted in FIGS.43A and 43B are embodiments of lesions that can be formed to interruptthe flow of current 950. As can be seen in the figures, this mitrallesion 975 connects to the box-like lesion 900 formed by the leftpulmonary vein lesion 901, the right pulmonary vein lesion 902 and theposterior wall lesion 903.

As depicted in FIG. 43A, in one embodiment, the mitral lesion 975extends from the vicinity of the mitral valve 960 (the mitral valveannulus) and intersects with the flow path of the current 950 and lesion900. In this and other embodiments, it important that the mitral lesion975 at least intersects with the flow path of the current 950 and lesion900. Therefore, the mitral lesion 975 can be formed at various locationswithin the left atrium as long as it intersects the flow path of thecurrent 950 and connects to lesion 900. This type of lesion can beformed by modifying the shape of the treatment section of the catheter.

In the embodiment depicted in FIG. 43B, the same loop-like treatmentsection of the catheter used to create the left pulmonary vein lesion901, the right pulmonary vein lesion 902 and the posterior wall lesion903 can be used to create the mitral lesion 975. As can be seen in FIG.43B, creating a loop-like or circular mitral lesion 975 cause the lesion975 to intersect the flow path of the current 950 and lesion 900 atmultiple points (A, B, C, D) thereby increasing the likelihood of asuccessful procedure.

If necessary, the mitral lesion 975 can be created after the box-likelesion 900 described above with respect to FIG. 41 is formed. A method1100 for performing a procedure that includes forming the mitral lesion975 as step 1090 after the box-like lesion 900 is formed is set forth inthe flow diagram shown in FIG. 44. It will be readily apparent to thoseskilled in the art that the steps used in the procedure for forming theleft pulmonary vein lesion 901, the right pulmonary vein lesion 902, theposterior wall lesion 903 and the mitral lesion 975 can be performed inany order as long as following the procedure, all the pulmonary veinentries are isolated and the flow path of current 950 is interrupted.

In another embodiment, in some patients that suffer from persistentatrial fibrillation, a linear lesion in the right atrium 2 may benecessary. As depicted in FIG. 45, this linear lesion 2500 is created toconnect the entrance of the Inferior Vena Cava (IVC) 6 b and the annulusof the Tricuspid Valve (TV) 2510 and extends through the Cava TricuspidIsthmus (CTI) 2520. This CTI lesion is used to prevent/interrupt themajority of potential re-entry circuits in the right atrium such as, forexample, right atrial flutter and/or other arrhythmias that originate inthe right atrium. This type of lesion is described in commonly assignedU.S. patent application Ser. No. 15/304,524, entitled “ENDOVASCULAR NEARCRITICAL FLUID BASED CRYOABLATION CATHETER HAVING PLURALITY OF PREFORMEDTREATMENT SHAPES,” filed Oct. 15, 2016 by Alexei Babkin, et al., thecontents of which is incorporated herein by reference in its entiretyfor all purposes.

In some embodiments, for certain patients, in addition to forming thelesions (901, 902, 903) discussed above with reference to FIGS. 39-41,it will be necessary to form the CTI lesion 2500 discussed above withreference to FIG. 45. It will be readily apparent to those skilled inthe art that the steps used in the procedure for forming the leftpulmonary vein lesion 901, the right pulmonary vein lesion 902, theposterior wall lesion 903 and the CTI lesion 2500 can be performed inany order as long as following the procedure, all the pulmonary veinentries are isolated and the majority of the potential re-entry circuitsin the right atrium are interrupted/prevented.

In some embodiments, for certain patients, in addition to forming thelesions (901, 902, 903) discussed above with reference to FIGS. 39-41and the mitral lesion 975 discussed above with reference to FIGS. 43A,43B and 44, it will be necessary to form the CTI lesion 2500 discussedabove with reference to FIG. 45. It will be readily apparent to thoseskilled in the art that the steps used in the procedure for forming theleft pulmonary vein lesion 901, the right pulmonary vein lesion 902, theposterior wall lesion 903, the mitral lesion 975 and the CTI lesion 2500can be performed in any order as long as following the procedure, allthe pulmonary vein entries are isolated, the flow path of current 950 isinterrupted and the majority of the potential re-entry circuits in theright atrium are interrupted/prevented.

Many modifications and variations of the present invention are possiblein light of the above teachings. It is therefore to be understood thatwithin the scope of the appended claims the invention may be practicedotherwise than as specifically described.

1. An ablation apparatus for creating a lesion in target tissue, theablation apparatus comprising: an ablation shaft comprising: a handle; afirst portion; an ablation portion; distal tip; at least one ablationenergy delivery lumen; at least one ablation energy return lumen; and astylet lumen that extends substantially along a length of the ablationshaft from the handle to at least the ablation portion; and a styletcapable of being inserted into the stylet lumen, the stylet comprising ashape-memory material.
 2. The ablation apparatus of claim 1, wherein theat least one ablation energy delivery lumen and the at least oneablation energy return lumen comprise an inner tube having an outer tubesurrounding the inner tube thereby defining a gap between the inner tubeand the outer tube.
 3. The ablation apparatus of claim 2, wherein thegap is capable of being filled with a thermally conducting media.
 4. Theablation apparatus of claim 1, wherein the ablation energy is providedby a cryogen.
 5. The ablation apparatus of claim 4, wherein the cryogenis nitrogen.
 6. The ablation apparatus of claim 5, wherein the nitrogenis near critical nitrogen.
 7. The ablation apparatus of claim 1, whereinthe shape memory material is Nitinol.
 8. An ablation apparatus forcreating a lesion in target tissue, the ablation apparatus comprising:an ablation shaft comprising: a handle; a first portion; an ablationportion; distal tip; at least one ablation energy delivery lumen; atleast one ablation energy return lumen; and a stylet lumen that extendssubstantially along a length of the ablation shaft from the handle to atleast the ablation portion; and a stylet capable of being inserted intothe stylet lumen, the stylet comprising a shape-memory material, whereinthe stylet has a plurality of flexibilities along its length.
 9. Theablation apparatus of claim 8, wherein the plurality of flexibilitiesare due to mechanical alterations to the stylet.
 10. The ablationapparatus of claim 8, wherein the ablation energy is provided bynitrogen.
 11. The ablation apparatus of claim 8, wherein the shapememory material is Nitinol.
 12. The ablation apparatus of claim 8,wherein at least a distal portion of the stylet is pre-set with a shapethat corresponds to a desired shape of the lesion to be formed.
 13. Anablation apparatus for creating a lesion in target tissue, the ablationapparatus comprising: an ablation shaft comprising: a handle; a firstportion; an ablation portion; a distal non-ablation portion; at leastone ablation energy delivery lumen; at least one ablation energy returnlumen; and a stylet lumen that extends substantially along a length ofthe ablation shaft from the handle to at least the ablation portion; anda stylet capable of being inserted into the stylet lumen, the styletcomprising a shape-memory material and having a distal portion that ispre-set with a shape that corresponds to (i) a desired shape of thelesion to be formed and (ii) a shape of a diagnostic portion, whereinthe diagnostic portion of the stylet corresponds to the distalnon-ablation portion of the ablation shaft.
 14. The ablation apparatusof claim 13, wherein the stylet has a plurality of differentflexibilities along its length.
 15. The ablation apparatus of claim 13,wherein the at least one ablation energy delivery lumen and the at leastone ablation energy return lumen comprise an inner tube having an outertube surrounding the inner tube thereby defining a gap between the innertube and the outer tube.
 16. The ablation apparatus of claim 14, whereinthe plurality of flexibilities are due to mechanical alterations to thestylet.
 17. A cryoablation catheter for creating a lesion in targettissue, the cryoablation catheter comprising: an ablation shaftcomprising: a handle; a freezing portion; a distal non-freezing portion;a plurality of cryogen delivery tubes, wherein each cryogen deliverytube comprises an inner tube having an outer tube surrounding the innertube thereby defining a gap between the inner tube and the outer tube; aplurality of cryogen return tubes, wherein each cryogen return tubecomprises an inner tube having an outer tube surrounding the inner tubethereby defining a gap between the inner tube and the outer tube; aplurality of electrodes on an exterior surface of the freezing portion;at least one service lumen; and a stylet lumen that extendssubstantially along a length of the ablation shaft from the handle to atleast the freezing portion; a stylet inserted into the stylet lumen, thestylet comprising a shape-memory material and having a distal portionthat is pre-set with a shape that corresponds to (i) a desired shape ofthe lesion to be formed and (ii) a shape of a diagnostic portion to bereceived within a pulmonary vein entry, wherein the diagnostic portionof the stylet corresponds to the distal non- freezing portion of theablation shaft.
 18. The cryoablation catheter of claim 17, wherein thecryogen is nitrogen.
 19. The cryoablation catheter of claim 17, whereinthe shape memory material is Nitinol.
 20. An ablation apparatus forcreating a lesion in target tissue, the ablation apparatus comprising:an ablation shaft comprising: a handle; a first portion; an ablationportion; a non-ablation distal portion; at least one ablation energydelivery lumen; at least one ablation energy return lumen; and a styletlumen that extends substantially along a length of the ablation shaftfrom the handle to at least the ablation portion; and a stylet capableof being inserted into the stylet lumen, the stylet comprising ashape-memory material and having a distal portion that is pre-set with ashape that corresponds to (i) a desired shape of the lesion to be formedand (ii) a shape of a diagnostic portion, wherein the diagnostic portionof the stylet corresponds to the distal non-ablation portion of theablation shaft, wherein the stylet has a plurality of flexibilitiesalong its length, and wherein the plurality of flexibilities are due tomechanical alterations to the stylet.